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This study examined to evaluate the predictive value of a nomogram with Ki-67 in overall and disease-free survival in glioma patients, a total of 76 patients diagnosed with glioma by pathology in Tengzhou Central People's Hospital were enrolled. The baseline data and follow ups were retrospectively collected from medical records. The associations between Ki-67 and survival status were examined using log-rank test, univariate and multivariate Cox proportional hazard regression models. Calibrations were performed to validate the established nomograms. Ki-67 negative group showed of a longer OS survival time and a longer PFS survival time with log-rank test (x2 = 16.101, P < 0.001 and x2 = 16.961, P < 0.001). Age older than 50 years (HR = 2.074, 95% CI 1.097–3.923), abnormal treatment (HR = 2.932, 95% CI 1.343–6.403) and Ki-67 positive (HR = 2.722, 95% CI 1.097–6.755) were the independent predictive factors of death. High grade pathology (HR = 2.453, 95% CI 1.010–5.956) and Ki-67 positive (HR = 2.200, 95% CI 1.043–4.639) were the independent predictive factors of recurrence. The C-index for the nomogram of OS and PFS were 0.745 and 0.723, respectively. The calibration results showed that the nomogram could predict the overall and disease-free 1-year survival of glioma patients. In conclusion, the nomograms with Ki-67 as independent risk factor for OS and PFS could provide clinical consultation in the treatment and follow-up of malignant glioma. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemotherapy (NACT) affects the tumor protein marker's expression and status. Changes in the expression of biomarkers during NACT may influence the clinical decision of adjuvant molecular and hormonal therapy. Hence, re-evaluation of receptor status has to be done after NACT to give a specific adjuvant therapy for patient benefit. Aims and Objectives: The aim of this study was to study the status of hormone receptors (HRs) - estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (Her-2/Neu), and Ki-67 in patients with locally advanced breast cancer (LABC) in both core needle biopsies and post-mastectomy specimens after administering neoadjuvant chemotherapy. Materials and Methods: The present study was conducted in the Department of Pathology in collaboration with the Department of Surgery, Pt B D Sharma PGIMS, Rohtak, for a period of 1 year. The study comprised 52 patients with LABC who received neoadjuvant chemotherapy and 20 control cases who did not receive neoadjuvant chemotherapy. Each case comprised two specimens: Trucut biopsy and a mastectomy specimen. Results: ER changed from positive to negative in 15.4% of the cases and from negative to positive in 1.9% of the cases. The overall change in ER was statistically significant (P=0.020). For PR, 9.6% of the cases changed from positive to negative while none of the cases showed change from negative to positive. The overall change in PR was statistically significant (P=0.025). For HER2/Neu, 19.2% of the cases changed from positive to negative, and 11.5% of the cases changed from negative to positive. The overall change in HER2/Neu was not statistically significant (P=0.317). For Ki-67, 30% of patients changed from positive to negative while 11.5% of patients changed from negative to positive. The overall change in Ki-67 was statistically significant (P=0.024). Conclusion: There was discordance in the HR status and proliferation marker after NACT in patients with breast cancer. The administration of NACT might be the main reason for the change in receptor status thus understanding the chemotherapy-induced biological conversion in the tumor cell behavior is strategically important in planning adjuvant endocrine therapy and for disease follow-up. [ABSTRACT FROM AUTHOR]

Background and Aim: Autotaxin (ATX) is an extracellular lysophospholipase D that catalyzes the hydrolysis of lysophosphatidylcholine into lysophosphatidic acid (LPA). Recent accumulating evidence indicates the biological roles of ATX in malignant tumors. However, the expression and clinical implications of ATX in human cholangiocarcinoma (CCA) remain elusive. Methods: In this study, the expression of ATX in 97 human CCA tissues was evaluated by immunohistochemistry. Serum ATX levels were determined in CCA patients (n = 26) and healthy subjects (n = 8). Autotaxin expression in cell types within the tumor microenvironment was characterized by immunofluorescence staining. Results: High ATX expression in CCA tissue was significantly associated with a higher frequency of lymph node metastasis (p = 0.050). High ATX expression was correlated with shorter overall survival (p = 0.032) and recurrence‐free survival (RFS) (p = 0.001) than low ATX expression. In multivariate Cox analysis, high ATX expression (p = 0.019) was an independent factor for shorter RFS. Compared with low ATX expression, high ATX expression was significantly associated with higher Ki‐67‐positive cell counts (p < 0.001). Serum ATX levels were significantly higher in male CCA patients than in healthy male subjects (p = 0.030). In the tumor microenvironment of CCA, ATX protein was predominantly expressed in tumor cells, cancer‐associated fibroblasts, plasma cells, and biliary epithelial cells. Conclusions: Our study highlights the clinical evidence and independent prognostic value of ATX in human CCA. [ABSTRACT FROM AUTHOR]

Purpose: To explore the value of deep learning-based multi-parametric magnetic resonance imaging (mp-MRI) nomogram in predicting the Ki-67 expression in rectal cancer. Methods: The data of 491 patients with rectal cancer from two centers were retrospectively analyzed and divided into training, internal validation, and external validation sets. They were categorized into high- and low-expression group based on postoperative pathological Ki-67 expression. Each patient's mp-MRI data were analyzed to extract and select the most relevant features of deep learning, and a deep learning model was constructed. Independent predictive risk factors were identified and incorporated into a clinical model, and the clinical and deep learning models were combined to obtain a nomogram for the prediction of Ki-67 expression. The performance characteristics of the DL-model, clinical model, and nomogram were assessed using ROCs, calibration curve, decision curve, and clinical impact curve analysis. Results: The strongest deep learning features were extracted and screened from mp-MRI data. Two independent predictive factors, namely Magnetic Resonance Imaging T (mrT) staging and differentiation degree, were identified through clinical feature selection. Three models were constructed: a deep learning (DL)-model, a clinical model, and a nomogram. The AUCs of clinical model in the training, internal validation, and external validation set were 0.69, 0.78, and 0.67, respectively. The AUCs of the deep model and nomogram ranged from 0.88 to 0.98. The prediction performance of the deep learning model and nomogram was significantly better than the clinical model (P < 0.001). Conclusion: The nomogram based on deep learning can help clinicians accurately and conveniently predict the expression status of Ki-67 in rectal cancer. [ABSTRACT FROM AUTHOR]

Background: Meningioma subtype is crucial in treatment planning and prognosis delineation, for grade 1 meningiomas. T2 relaxometry could provide detailed microscopic information but is often limited by long scanning times. Purpose: To investigate the potential of T2 maps derived from multiple overlapping‐echo detachment imaging (MOLED) for predicting meningioma subtypes and Ki‐67 index, and to compare the diagnostic efficiency of two different region‐of‐interest (ROI) placements (whole‐tumor and contrast‐enhanced, respectively). Study Type: Prospective. Phantom/Subjects: A phantom containing 11 tubes of MnCl2 at different concentrations, eight healthy volunteers, and 75 patients with grade 1 meningioma. Field Strength/Sequence: 3 T scanner. MOLED, T2‐weighted spin‐echo sequence, T2‐dark‐fluid sequence, and postcontrast T1‐weighted gradient echo sequence. Assessment: Two ROIs were delineated: the whole‐tumor area (ROI1) and contrast‐enhanced area (ROI2). Histogram parameters were extracted from T2 maps. Meningioma subtypes and Ki‐67 index were reviewed by a neuropathologist according to the 2021 classification criteria. Statistical Tests: Linear regression, Bland–Altman analysis, Pearson's correlation analysis, independent t test, Mann–Whitney U test, Kruskal–Wallis test with Bonferroni correction, and multivariate logistic regression analysis with the P‐value significance level of 0.05. Results: The MOLED T2 sequence demonstrated excellent accuracy for phantoms and volunteers (Meandiff = −1.29%, SDdiff = 1.25% and Meandiff = 0.36%, SDdiff = 2.70%, respectively), and good repeatability for volunteers (average coefficient of variance = 1.13%; intraclass correlation coefficient = 0.877). For both ROI1 and ROI2, T2 variance had the highest area under the curves (area under the ROC curve = 0.768 and 0.761, respectively) for meningioma subtyping. There was no significant difference between the two ROIs (P = 0.875). Significant correlations were observed between T2 parameters and Ki‐67 index (r = 0.237–0.374). Data Conclusion: MOLED T2 maps can effectively differentiate between meningothelial, fibrous, and transitional meningiomas. Moreover, T2 histogram parameters were significantly correlated with the Ki‐67 index. Level of Evidence: 1 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Background: Radiomics has been extensively applied in predicting Ki‐67 in breast cancer (BC). However, this is often confined to the exploration of a single sequence, without considering the varying sensitivity and specificity among different sequences. Purpose: To develop a nomogram based on dual‐sequence MRI derived radiomic features combined with clinical characteristics for assessing Ki‐67 expression in BC. Study Type: Retrospective. Population: 227 females (average age, 51 years) with 233 lesions and pathologically confirmed BC, which were divided into the training set (n = 163) and test set (n = 70). Field Strength/Sequence: 3.0‐T, T1‐weighted dynamic contrast‐enhanced MRI (DCE‐MRI) and apparent diffusion coefficient (ADC) maps from diffusion‐weighted MRI (EPI sequence). Assessment: The regions of interest were manually delineated on ADC and DCE‐MRI sequences. Three radiomics models of ADC, DCE‐MRI, and dsMRI (combined ADC and DCE‐MRI sequences) were constructed by logistic regression and the radiomics score (Radscore) of the best model was calculated. The correlation between Ki‐67 expression and clinical characteristics such as receptor status, axillary lymph node (ALN) metastasis status, ADC value, and time signal intensity curve was analyzed, and the clinical model was established. The Radscore was combined with clinical predictors to construct a nomogram. Statistical Tests: The independent sample t‐test, Mann–Whitney U test, Chi‐squared test, Interclass correlation coefficients (ICCs), single factor analysis, least absolute shrinkage and selection operator (LASSO), logistic regression, receiver operating characteristics, Delong test, Hosmer_Lemeshow test, calibration curve, decision curve. A P‐value <0.05 was considered statistically significant. Results: In the test set, the prediction efficiency of the dsMRI model (AUC = 0.862) was higher than ADC model (AUC = 0.797) and DCE‐MRI model (AUC = 0.755). With the inclusion of estrogen receptor (ER) and ALN metastasis, the nomogram displayed quality improvement (AUC = 0.876), which was superior to the clinical model (AUC = 0.787) and radiomics model. Data Conclusion: The nomogram based on dsMRI radiomic features and clinical characteristics may be able to assess Ki‐67 expression in BC. Level of Evidence: 3 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

Purpose: To develop a nomogram using clinical features and the MRI parameters for preoperatively predicting the expression of Ki-67 in patients with hepatocellular carcinoma (HCC). Methods: One hundred and forty patients (training cohorts: n = 108; validation cohorts: n = 32) with confirmed HCC were investigated. Mann–Whitney U test, independent sample t-test, and chi-squared test were used to analyze the continuous and categorical variables. Univariate and multivariate logistic regression analyses were performed to examine the clinical variables and parameters from MRI associated with Ki-67 expression. As a result, a nomogram was developed based on these associations in patients with HCC. The performance of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration curves. Results: In the training set, multivariable logistic regression analysis revealed that lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) levels, protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels, and tumor shape were independent predictors for Ki-67 expression (p < 0.05). These three variables and the apparent diffusion coefficient (ADC) value were used to establish a nomogram, while the ADC value was found to be a marginal significant predictor. The model demonstrated a strong ability to discriminate Ki-67 expression in both the training and validation cohorts (AUC = 0.862, 0.877). Conclusion: A non-invasive preoperative prediction method, which incorporates MRI variables and clinical features was developed, and showed effectiveness in evaluating Ki-67 expression in HCC patients. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to assess the diagnostic value of ultrasound habitat sub-region radiomics feature parameters using a fully connected neural networks (FCNN) combination method L2,1-norm in relation to breast cancer Ki-67 status. Methods: Ultrasound images from 528 cases of female breast cancer at the Affiliated Hospital of Xiangnan University and 232 cases of female breast cancer at the Affiliated Rehabilitation Hospital of Xiangnan University were selected for this study. We utilized deep learning methods to automatically outline the gross tumor volume and perform habitat clustering. Subsequently, habitat sub-regions were extracted to identify radiomics features and underwent feature engineering using the L1,2-norm. A prediction model for the Ki-67 status of breast cancer patients was then developed using a FCNN. The model's performance was evaluated using accuracy, area under the curve (AUC), specificity (Spe), positive predictive value (PPV), negative predictive value (NPV), Recall, and F1. In addition, calibration curves and clinical decision curves were plotted for the test set to visually assess the predictive accuracy and clinical benefit of the models. Result: Based on the feature engineering using the L1,2-norm, a total of 9 core features were identified. The predictive model, constructed by the FCNN model based on these 9 features, achieved the following scores: ACC 0.856, AUC 0.915, Spe 0.843, PPV 0.920, NPV 0.747, Recall 0.974, and F1 0.890. Furthermore, calibration curves and clinical decision curves of the validation set demonstrated a high level of confidence in the model's performance and its clinical benefit. Conclusion: Habitat clustering of ultrasound images of breast cancer is effectively supported by the combined implementation of the L1,2-norm and FCNN algorithms, allowing for the accurate classification of the Ki-67 status in breast cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: Ki-67 is recommended by international/national guidelines for risk stratification in early breast cancer (EBC), particularly for defining "intermediate risk," despite inter-laboratory/inter-observer variability and cutoff uncertainty. We investigated Ki-67 (> 10%– < 40%, determined locally) as a prognostic marker for intermediate/high risk in EBC, pN0-1 patients. Methods: This prospective, non-interventional, real-world study included females ≥ 18 years, with pN0/pN1mi/pN1, HR+ , HER2-negative EBC, and locally determined Ki-67 ranging 10%–40%. The primary outcome was changes in treatment recommendations after disclosing the Oncotype DX Breast Recurrence Score®(RS) assay result. Results: The analysis included 567 patients (median age, 57 [range, 29–83] years; 70%/1%/29%/ with pN0/pN1mi/pN1 disease; 81% and 19% with RS results 0–25 and 26–100, respectively). The correlations between local and central Ki-67, local Ki-67, and the RS, and central Ki-67 and the RS results were weak (r = 0.35, r = 0.3, and r = 0.46, respectively), and discrepancies were noted in both directions (e.g., local Ki-67 was lower or higher than central Ki-67). After disclosing the RS, treatment recommendations changed for 190 patients (34%). Changes were observed in pN0 and pN1mi/pN1 patients and in patients with centrally determined Ki-67 ≤ 10% and > 10%. Treatment changes were aligned with RS results (adding chemotherapy for patients with higher RS results, omitting it for lower RS results), and their net result was 8% reduction in adjuvant chemotherapy use (from 32% pre-RS results to 24% post-RS results). Conclusion: The Oncotype DX® assay is a tool for individualizing treatments that adds to classic treatment decision factors. The RS result and Ki-67 are not interchangeable, and Ki-67, as well as nodal status, should not be used as gatekeepers for testing eligibility, to avoid under and overtreatment. [ABSTRACT FROM AUTHOR]

Objective: To assess whether diffusion and perfusion MRI derived parameters could non-invasively predict PD-L1 and Ki-67 status in primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL). Methods: We retrospectively analyzed DWI, DSC-PWI, and morphological MRI (mMRI) in 88 patients with PCNS-DLBCL. The mMRI features were compared using chi-square tests or Fisher exact test. Minimum ADC (ADCmin), mean ADC(ADCmean), relative minimum ADC (rADCmin), relative mean ADC (rADCmean), and relative maximum CBV (rCBVmax) values were compared in PCNS-DLBCL with different molecular status by using the Mann-Whitney U test. The diagnostic performances were evaluated by receiver operating characteristic curves. Results: PCNS-DLBCL with high PD-L1 expression demonstrated a significantly higher ADCmin value than those with low PD-L1. The ADCmean and rADCmean values were significantly lower in PCNS-DLBCL with high Ki-67 status compared with those in low Ki-67 status. Other ADC, CBV parameters, and mMRI features did not show any association with these molecular statuses The diagnostic efficacy of ADC values in assessing PD-L1 and Ki-67 status was relatively low, with area under the curves (AUCs) values less than 0.7. Conclusions: DWI-derived ADC values can provide some relevant information about PD-L1 and Ki-67 status in PCNS-DLBCL, but may not be sufficient to predict their expression due to the rather low diagnostic performance. [ABSTRACT FROM AUTHOR]

Background: Myxofibrosarcoma is a myxoid soft tissue sarcoma showing T2 high intensity on magnetic resonance imaging. However, myxofibrosarcoma is a heterogeneous sarcoma with both myxoid and cellular portions. Magnetic resonance imaging findings were obtained MRI findings for comparison with histological and Ki-67 immunohistochemical features, in different portions of one myxofibrosarcoma. Case presentation: Magnetic resonance imaging observations were compared with gross pathological and microscopic findings of a myxofibrosarcoma from a 50-year-old Japanese female. The Ki-67 labeling indices of different portions of the tumor, that is, the myxoid, cellular, and histologically confirmed infiltrative margin portions (pathological tail sign), were compared. The T2 low intensity area was more cellular than the T2 high intensity area, while the cellular portion had a significantly higher Ki-67 index than the myxoid portion (p = 0.0313). The portions with the pathological tail sign had a significantly higher Ki-67 labeling index than those without this sign (p = 0.0313). Conclusions: More cellular portions of a myxofibrosarcoma correspond to more areas of the tumor showing aggressive features. Furthermore, our data also support the hypothesis of high aggressiveness being associated with the pathological tail sign in myxofibrosarcoma. To our knowledge, this is the first case report to describe comparisons among the imaging findings, histological features, and Ki-67 immunohistochemistry results for different portions of one myxofibrosarcoma. [ABSTRACT FROM AUTHOR]

Background: Vascular invasion (VI) is closely related to the metastasis, recurrence, prognosis, and treatment of gastric cancer. Currently, predicting VI preoperatively using traditional clinical examinations alone remains challenging. This study aims to explore the value of radiomics analysis based on preoperative enhanced CT images in predicting VI in gastric cancer. Methods: We retrospectively analyzed 194 patients with gastric adenocarcinoma who underwent enhanced CT examination. Based on pathology analysis, patients were divided into the VI group (n = 43) and the non-VI group (n = 151). Radiomics features were extracted from arterial phase (AP) and portal venous phase (PP) CT images. The radiomics score (Rad-score) was then calculated. Prediction models based on image features, clinical factors, and a combination of both were constructed. The diagnostic efficiency and clinical usefulness of the models were evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Results: The combined prediction model included the Rad-score of AP, the Rad-score of PP, Ki-67, and Lauren classification. In the training group, the area under the curve (AUC) of the combined prediction model was 0.83 (95% CI 0.76–0.89), with a sensitivity of 64.52% and a specificity of 92.45%. In the validation group, the AUC was 0.80 (95% CI 0.67–0.89), with a sensitivity of 66.67% and a specificity of 88.89%. DCA indicated that the combined prediction model might have a greater net clinical benefit than the clinical model alone. Conclusion: The integrated models, incorporating enhanced CT radiomics features, Ki-67, and clinical factors, demonstrate significant predictive capability for VI. Moreover, the radiomics model has the potential to optimize personalized clinical treatment selection and patient prognosis assessment. [ABSTRACT FROM AUTHOR]

Objective To detect the expression levels of Ki-67 and isocitrate dehydrogenase 1-R132 H (IDH1-R132 H) in central nervous system glioma cells and to explore their clinical significance. Methods A total of 41 patients with surgically resected and pathologically confirmed brain gliomas were included in this study. Thirteen normal brain tissue samples obtained from patients undergoing craniotomy for head trauma and spontaneous intracerebral hemorrhage were used as a control group. Immunohistochemistry was employed to detect and compare the protein expression levels of Ki-67 and IDH1-R132 H in glioma and control groups. Results The positive rate of Ki-67 in grade Ⅲ-Ⅳ tumors (93.7%) was significantly higher than that in grade Ⅰ-Ⅱ tumors (45.4%), with a statistically significant difference between the two groups (χ²=11.748, P＜0.05). Ki-67 was not expressed in normal brain tissue. The positive rate of IDH1-R132 H in grade Ⅱ and Ⅲ tumors (83.3%) was significantly higher than that in grade I and IV tumors (47.0%), with a statistically significant difference between the two groups (χ²=6.047, P＜0.05). IDH1-R132 H was not expressed in normal brain tissue. There was a statistically significant difference in Ki-67 expression between the IDH1-R132 H negative and positive groups (χ~2=4.055, P＜0.05), with a significant negative correlation (r=-0.314, P＜0.05). Conclusion The expression levels of Ki-67 and IDH1-R132 H can guide clinical practice in patients with gliomas, providing a certain reference basis. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) poses a significant global health concern, ranking as the fourth most frequently diagnosed cancer and the fourth leading cause of death among women worldwide. Ecuador bears a substantial burden of CC, with a considerable number of new cases and deaths reported annually. The primary cause of CC is the human papillomavirus (HPV), a sexually transmitted virus that is usually eliminated by cell immunity. However, around 5% of infections persist and can lead to invasive cancer. This literature review assessed the predictive value of p16 and Ki-67 dual staining (DS) as a standalone method or combined with conventional triage methods to improve CC screening programs. A total of 42 relevant articles were analyzed, evaluating the performance of DS in predicting cervical intraepithelial neoplasia (CIN) of varying severities. DS exhibited a median sensitivity and specificity of 87.7% and 76.7% for detecting CIN2+ and 89.7% and 79.6% for CIN3+. When combined with liquid-based (LB) cytology, DS demonstrated superior sensitivity and specificity compared to other screening strategies. This review suggests that p16 and Ki-67 DS alone or in combination with liquid base (LB) could enhance the accuracy and effectiveness of CC screening. [ABSTRACT FROM AUTHOR]

Objective To investigate the relationship between expression levels of epidermal growth factor receptor (EGFR), proliferation marker protein Ki-67 (Ki-67), P53 and circulating tumor cell (CTC) and the prognosis of triple negative breast cancer. Methods A total of 95 patients with triple negative breast cancer were selected. The expression levels of EGFR, Ki-67 and P53 in pathological tissue specimens were detected by immunohistochemistry. All patients underwent 8 cycles of chemotherapy, and the expression of CTC was detected before and after chemotherapy by isolation epithelial tumor cells (ISET). The relationship between CTC expression before and after chemotherapy and efficacy of chemotherapy was analyzed. The correlation between CTC and expression levels of EGFR, Ki-67 and P53 was analyzed. Patients were followed up for progression free survival (PFS). Risk factors of progression for triple negative breast cancer were analyzed by COX regression. Results The positive detection rates of EGFR, Ki-67 and P53 were 44.21% (42/95), 63.16% (60/95) and 56.84% (54/95). The positive detection rate of CTC was lower in patients after chemotherapy than that before chemotherapy (14.74% vs. 61.05%, P＜0.05). The efficacy of chemotherapy was negatively correlated with the positive expression of CTC after chemotherapy (P＜0.001). COX regression analysis found that clinical stage Ⅲ, positive EGFR and CTC after chemotherapy were independent risk factors of progression of triple negatively breast cancer (P＜0.05). PFS of patients at clinical stage Ⅰ, stage Ⅱ, and stage Ⅲ decreased in order (P＜0.05). PFS of EGFR positive patients was shorter than that of EGFR negative patients (P＜0.05). PFS of CTC positive patients after chemotherapy was shorter than that of CTC negative patients after chemotherapy (P＜0.05). Conclusion The positive expression of EGFR before chemotherapy and the positive expression of CTC after chemotherapy are related to the poor survival prognosis of patients with triple negative breast cancer. The lower the positive detection rate of CTC after chemotherapy, the better the efficacy of chemotherapy. [ABSTRACT FROM AUTHOR]

Gliomas are the most common primary brain tumours and constitute approximately half of all malignant glioblastomas. Unfortunately, patients diagnosed with malignant glioblastomas typically survive for less than a year. In light of this circumstance, genotyping is an effective means of categorising gliomas. The Ki67 proliferation index, a widely used marker of cellular proliferation in clinical contexts, has demonstrated potential for predicting tumour classification and prognosis. In particular, magnetic resonance imaging (MRI) plays a vital role in the diagnosis of brain tumours. Using MRI to extract glioma-related features and construct a machine learning model offers a viable avenue to classify and predict the level of Ki67 expression. This study retrospectively collected MRI data and postoperative immunohistochemical results from 613 glioma patients from the First Affliated Hospital of Nanjing Medical University. Subsequently, we performed registration and skull stripping on the four MRI modalities: T1-weighted (T1), T2-weighted (T2), T1-weighted with contrast enhancement (T1CE), and Fluid Attenuated Inversion Recovery (FLAIR). Each modality's segmentation yielded three distinct tumour regions. Following segmentation, a comprehensive set of features encompassing texture, first-order, and shape attributes were extracted from these delineated regions. Feature selection was conducted using the least absolute shrinkage and selection operator (LASSO) algorithm with subsequent sorting to identify the most important features. These selected features were further analysed using correlation analysis to finalise the selection for machine learning model development. Eight models: logistic regression (LR), naive bayes, decision tree, gradient boosting tree, and support vector classification (SVM), random forest (RF), XGBoost, and LightGBM were used to objectively classify Ki67 expression. In total, 613 patients were enroled in the study, and 24,455 radiomic features were extracted from each patient's MRI. These features were eventually reduced to 36 after LASSO screening, RF importance ranking, and correlation analysis. Among all the tested machine learning models, LR and linear SVM exhibited superior performance. LR achieved the highest area under the curve score of 0.912 ± 0.036, while linear SVM obtained the top accuracy with a score of 0.884 ± 0.031. This study introduced a novel approach for classifying Ki67 expression levels using MRI, which has been proven to be highly effective. With the LR model at its core, our method demonstrated its potential in signalling a promising avenue for future research. This innovative approach of predicting Ki67 expression based on MRI features not only enhances our understanding of cell activity but also represents a significant leap forward in brain glioma research. This underscores the potential of integrating machine learning with medical imaging to aid in the diagnosis and prognosis of complex diseases. [ABSTRACT FROM AUTHOR]

Morphological and immunohistochemical studies of solid arrangement canine mammary carcinomas have shown that the different histological types may be characterized by proliferation of epithelial and/or myoepithelial cells. However, little is known about immunophenotypes and the importance of inflammation as prognostic factors in these neoplasms. The objective of the present study was to characterize the immunophenotype and degree of inflammation in the solid type of canine mammary neoplasm and to investigate their association with metastasis, Ki-67 index, tumour size, necrosis and survival. Sixty-five carcinomas with solid pattern, basaloid carcinomas, solid papillary carcinomas, malignant adenomyoepitheliomas (MAMEs) or malignant myoepitheliomas (MMEs) were investigated. Luminal A, luminal B HER2 negative and HER2 positive, HER2 overexpressed and triple negative immunophenotypes were immunolabelled as were Ki-67 protein and cyclooxygenase-2 (Cox-2). Histological peritumoural and intratumoural inflammatory infiltrates were graded (distribution × intensity) and the presence of necrosis identified. We found a statistical difference between histological types and immunophenotypes, with MME and MAME having a higher occurrence of luminal A, whereas most neoplasms had the luminal B HER-negative immunophenotype. There was no correlation between immunophenotype and degree of peri- and intratumoural inflammation, nodal metastasis, necrosis or tumour size. An increased degree of peri- and intratumoural inflammation was significantly associated with lymph node metastasis, and more severe intratumoural inflammation was associated with the presence of tumour necrosis. Tumour size, Ki-67 index and Cox-2 score were not associated with inflammation in either peri- or intratumoural regions. No difference was observed in survival in relation to immunophenotype or degree of inflammation, but the Cox regression model revealed that nodal metastasis influenced the risk of death. [ABSTRACT FROM AUTHOR]

Purpose: Diffuse gliomas present a significant challenge for healthcare systems globally. While brain MRI plays a vital role in diagnosis, prognosis, and treatment monitoring, accurately characterizing gliomas using conventional MRI techniques alone is challenging. In this study, we explored the potential of utilizing the amide proton transfer (APT) technique to predict tumor grade and type based on the WHO 2021 Classification of CNS Tumors. Methods: Forty-two adult patients with histopathologically confirmed brain gliomas were included in the study. They underwent 3T MRI imaging, which involved APT sequence. Multinomial and binary logistic regression models were employed to classify patients into clinically relevant groups based on MRI findings and demographic variables. Results: We found that the best model for tumor grade classification included patient age along with APT values. The highest sensitivity (88%) was observed for Grade 4 tumors, while Grade 3 tumors showed the highest specificity (79%). For tumor type classification, our model incorporated four predictors: APT values, patient's age, necrosis, and the presence of hemorrhage. The glioblastoma group had the highest sensitivity and specificity (87%), whereas balanced accuracy was the lowest for astrocytomas (0.73). Conclusion: The APT technique shows great potential for noninvasive evaluation of diffuse gliomas. The changes in the classification of gliomas as per the WHO 2021 version of the CNS Tumor Classification did not affect its usefulness in predicting tumor grade or type. [ABSTRACT FROM AUTHOR]

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This research letter discusses the assessment of Ki-67 and mitoses in pituitary neuroendocrine tumors (PitNETs). The study found that there is an inverse relationship between the number of PitNET cells assessed and the Ki-67 proliferative index (PI) obtained. The authors suggest that digital Ki-67 PI and mitotic counts may have limited clinical value and question their efficacy as stand-alone tools for histopathological assessment and prognostication of PitNETs. They recommend consistent Ki-67 scoring approaches and re-evaluation of the recommended Ki-67 PI 3% cut-off to clarify this controversial topic. [Extracted from the article]

OBJECTIVE: Colorectal cancer, one of the most frequently diagnosed cancers worldwide, has a high mortality rate. Thus, our research aims to examine the preventive effects of diosmin (DIO) alone and in conjunction with the anti-cancer drug irinotecan (camptothecin- 11, CPT-11), on 1,2-dimethylhydrazine (DMH)-induced colon cancer (CC) in male Wistar rats. MATERIALS AND METHODS: Fifty adult male Wistar rats were categorized into five groups. Group I (Normal) received saline 0.9 orally % as a vehicle once a week for 14 weeks. Group II (DMH) received DMH (20 mg/kg/week) orally dissolved in 0.9% saline for 14 weeks and 1% carboxymethylcellulose (CMC) every other day for the final 10 weeks. Group III (DMH+DIO) received DMH orally for 14 weeks and DIO (10 mg/kg, suspended in 1% CMC) every other day for the fi- nal 10 weeks. Group IV (DMH+CPT-11) received DMH orally for 14 weeks and intraperitoneal injection of CPT-11 (3 mg/kg) twice a week for the final 10 weeks. Group V (DMH+DIO+CPT-11) orally received DMH for 14 weeks and both DIO and CPT-11. RESULTS: All treated groups showed a significant reduction (p<0.05) in their elevated serum malondialdehyde levels and significant amelioration (p<0.05) of their lowered activities of colon glutathione-S-transferase (GST) and glutathione reductase (GR) as well as serum glutathione level (GSH). In addition, simultaneous treatment with DIO and CPT-11 led to a significant decrease (p<0.05) in the elevated serum levels of carcinoembryonic antigen (CEA) in rats administered with DMH, as well as a reduction in the colon expression levels of the inflammatory mediator (NF-κB), cell proliferator protein (Ki-67), and proapoptotic protein (p53). CONCLUSIONS: These findings suggest DIO, CPT-11, and their combination have anticarcinogenic effects against DMH-induced CC by suppressing oxidative stress, simulating the antioxidant defense system, attenuating the inflammatory effects, and reducing cell proliferation. [ABSTRACT FROM AUTHOR]

Background: Immunohistochemistry (IHC) is widely used in the management of patients with cervical intraepithelial neoplasia (CIN) but still has many limitations in clinical practice. We analyzed the correlation of new biomarkers with the severity of CIN and follow-up outcomes in patients after conization to improve the management of patients with CIN. Methods: IHC staining of Eag1 and p16/Ki-67 was performed on cervical tissue sections from 234 patients with suspected CIN2/3. After a series of follow-ups, including human papillomavirus (HPV) test and thinprep cytologic test (TCT) for 1–2 years, the outcomes were collected. IHC scores of biomarkers and follow-up results were used to analyze the correlation and assess the diagnostic efficiency of biomarkers. Results: The IHC staining intensity of Eag1 and p16/Ki-67 was significantly different from that of the CIN1-3 groups (p < 0.05). Eag1 expression scores were significantly different in the distribution between the two follow-up groups (p < 0.001). ROC curves based on the correlations between the follow-up outcomes and the Eag1 scores and IS of p16/ki-67 showed that Eag1 had a greater AUC (0.767 vs. 0.666). Logistic regression analysis of the combination of biomarkers revealed a greater AUC value than any single biomarker. Conclusions: Eag1 expression was significantly correlated with CIN grade and follow-up outcomes after conization. IHC staining of combinations of biomarkers of Eag1, p16 and Ki-67 may help us to improve the ability to identify risk groups with abnormal follow-up outcomes after treatment for CIN. [ABSTRACT FROM AUTHOR]

Aim: Tumor Ki‐67 expression reflects prognosis and cancer grade, and biopsy‐based preoperative assessment of Ki‐67 expression is key to treatment. Apparent diffusion coefficient (ADC) values obtained with this imaging may noninvasively predict Ki‐67 by reflecting tumor cell density and limited water molecule movement from irregular alignment. This study aimed to investigate the ability of ADC values to predict Ki‐67 expression in intrahepatic cholangiocarcinoma (ICC). Method: We retrospectively analyzed 39 cases of ICC confirmed by surgical pathology. All patients had undergone magnetic resonance imaging, and ADC values (mean, minimum, and maximum) were calculated. Ki‐67 expression was assessed by immunohistochemistry, and patients were divided into groups of high (n = 18) and low (n = 21) Ki‐67 expression. To assess the diagnostic performance of the ADC values for Ki‐67 expression, we used the receiver operating characteristic curve and compared the areas under the curve (AUC). Results: The mean and minimum ADC values were significantly lower in the group with high Ki‐67 expression. For predicting high Ki‐67 expression, the AUC values were 0.701 for mean ADC, 0.818 for minimum ADC, and 0.571 for maximum ADC. The diagnostic sensitivity and specificity of the minimum ADC values were 88.9% and 76.2%, respectively. In addition, with ADC values combined, the AUC increased to 0.831. Apparent diffusion coefficient is a useful predictor of Ki‐67 expression level in ICC. Conclusion: Apparent diffusion coefficient values, especially minimum ADC values, can noninvasively predict ICC associated with high Ki‐67 expression. [ABSTRACT FROM AUTHOR]

Ki‐67, a nuclear protein expressed in all stages of cellular proliferation, is a valuable tool to assess tumor proliferation and has been linked to more aggressive tumor behavior. However, interlaboratory staining heterogeneity and inter‐observer variability challenge its reproducibility. Round Robin tests are a suitable tool to standardize and harmonize immunohistochemical and molecular analyses in histopathology. The study investigates the interrater and interlaboratory reproducibility of Ki‐67‐scoring using both manual and automated approaches. Unstained TMA slides comprising diverse tumor types (breast cancer, neuroendocrine tumors, lymphomas, and head and neck squamous cell carcinoma) were distributed to six pathology laboratories, each employing their routine staining protocols. Manual and automated scoring methods were applied, and interrater and interlaboratory agreement assessed using intraclass correlation coefficients (ICC). The results highlight good‐to‐excellent reliability overall, with automated scoring demonstrating higher consistency (ICC 0.955) than manual scoring (ICC 0.871). Results were more variable when looking at the individual entities. Reliability remained good for lymphomas (ICC 0.878) and breast cancer (ICC 0.784) and was poor in well‐differentiated neuroendocrine tumors (ICC 0.354). This study clearly advocates standardized practices and training to ensure consistency in Ki‐67‐assessment, and it demonstrates that this can be achieved in a peer‐to‐peer approach in local quality‐circles. [ABSTRACT FROM AUTHOR]

Objective: Neoadjuvant chemotherapy (NAC) in breast cancer (BC) is being considered for a broader range of cases, including locally advanced tumors and situations where downstaging could reduce extensive surgery. Several trials have explored predictive markers of pathological complete response (pCR). The role of Ki-67 as a predictor of pCR has been demonstrated in studies. However, the cut-off remains vague, given the lack of standardization of measurement methods. The aim of our study was to evaluate the predictive value of Ki-67 in response to NAC and to identify the cut-off values that exhibit the strongest correlation with best response. Materials and Methods: This retrospective study included 187 patients who had undergone surgery following NAC for BC at the CHU Souss Massa of Agadir between January 2020 and January 2023. Logistic regression was used to assess the correlation between Ki-67 and patients' characteristics. Optimal Ki-67 cutoff was identified by receiver operating characteristic curve. Kaplan-Meier curves were used to assess disease-free survival (DFS), and survival comparisons were assessed with the log-rank test. Results: The median age was 51.8±10.7 years and 51.4% of tumors were smaller than 5 cm. Node invasion was found in 55.4%. Luminal B subtype was found in 49.7%, followed by human epidermal growth factor receptor-2 (HER-2)-positive in 27.4%, triple-negative in 14.3% and Luminal A in 8.6%. pCR occurred in 40% of patients overall. Subgroup analysis revealed a significant association between pCR and tumor size (p<0.001), lymph node involvement (p<0.001), grade 2 (p<0.001), vascular invasion (p<0.001), and positive HER-2 status (p = 0.022). In statistical analysis, pathological responses were improved in patients with Ki-67 >35% (p<0.001). DFS was 98.8% at 12 months. No statistical difference was found in DFS according to Ki-67 values and pCR status. Conclusion: Our results indicate that Ki-67 is a predictive marker for response in the neoadjuvant setting in BC patients. Our study showed that a Ki-67 cut-off >35% predicts a better pCR rate in response to NAC. However, this cutoff value remains controversial due to the absence of a standard method of measurement, with inter- and intra-observer variability. It would be necessary to validate this cutoff in other studies. [ABSTRACT FROM AUTHOR]

Minichromosome maintenance (MCM) protein 2 is critical for the beginning of DNA replication and is a notable marker for proliferating cells. The prognosis and management of ameloblastoma are based on histology and other factors. However, immunohistologic markers capable of detecting recurrence-prone ameloblastoma with a poor prognosis have not been adequately investigated. This study aimed to identify the association between MCM2 overexpression and recurrence prognosis and risk stratification. Thirty-two patients who had been diagnosed with ameloblastoma at our department between January 1982 and December 2019 were included in this study. Thirty-two (fifteen follicular, ten plexiform, five unicystic, two desmoplastic) subtype cases were analyzed for immunohistochemical expressions of MCM2 and Ki-67. Disease-free survival (DFS) analysis revealed that patients with MCM2high/Ki-67high ameloblastoma had a significantly shorter median survival time (63 vs. 360 months) and lower DFS survival rate (50.0% vs. 90.0%) than those with MCM2low/Ki-67low (p = 0.003). Multivariate analysis revealed that a location (maxillary primary ameloblastoma) and MCM2high/Ki-67high were independent risk factors for DFS. Our results identified MCM2high/Ki-67high ameloblastoma as a subgroup with poor recurrent prognosis and DFS. Ameloblastoma should be assessed using immunohistochemical staining. Our study revealed that tumors with a worse recurrent prognosis require appropriate clinical surveillance. [ABSTRACT FROM AUTHOR]

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Background/Aim: Hyperthermia represents an adjuvant local anticancer strategy which relies on the increase of temperature beyond the physiological level. In this study, we investigated the anticancer potential of Fe3O4 and Fe3O4core Aushell nanoparticles as hyperthermic agents in terms of cytotoxicity and studied the expression of cellular markers of proliferation (changes in mRNA levels via realtime polymerase chain reaction). Materials and Methods: The human breast cancer cell line SK-BR-1 was incubated with either Fe3O4 or Fe3O4core Aushell nanoparticles stabilized with tryptophan, prior to hyperthermia treatment. The normal HEK293 cell line was used as a control. Toxicity was determined using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay to estimate possible toxic effects of the tested nanoparticles. After RNA extraction and cDNA synthesis, mRNA expression of three indicators of proliferation, namely marker of proliferation Ki-67, DNA topoisomerase II alpha (TOP2A) and TPX2 microtubule nucleation factor (TPX2), was investigated. Results: At each concentration tested, Fe3O4core Aushell nanoparticles showed greater toxicity compared to Fe3O4, while SK-BR-3 cells were more susceptible to their cytotoxic effects compared to the HEK293 cell line. The expression of Ki-67, TOP2A and TPX2 was reduced in SK-BR-3 cells by both Fe3O4 or Fe3O4core Aushell nanoparticles compared to untreated cells, while the only observed change in HEK293 cells was the up-regulation of TOP2A. Conclusion: Both Fe3O4core Aushell and Fe3O4 NPs exhibit increased cytotoxicity to the cancer cell line tested (SK-BR-3) compared to HEK293 cells. The down-regulation in SK-BR-3 cells of the three proliferative markers studied, Ki-67, TOP2A and TPX2, after incubation with NPs suggests that cells that survived thermal destruction were not actively proliferating. [ABSTRACT FROM AUTHOR]

Canine splenic hemangiosarcoma has a high metastatic rate and short survival time. Currently, the main prognostic parameters are tumor stage and therapy, while data on histologic parameters, such as grade and Ki-67 expression, are scarce. The aims of this study were to compare two methods of assessment of Ki-67, verify their prognostic impact, and define a threshold value based on survival. Thirty-one cases of histologically diagnosed canine splenic hemangiosarcoma, which were treated with splenectomy and had full staging and follow-up information, were collected. Three were stage I, 17 stage II, and 11 stage III. The mean mitotic count (MC) was 23.9 (standard deviation [SD]: 22.1) and the median was 15 (range, 1–93). Immunohistochemistry for Ki-67 was performed, the Ki-67 labeling index (Ki-67LI) was assessed as a percentage of positive neoplastic nuclei per ≥500 cell, and the Ki-67 count (KI-67C) was defined as the average number of positive nuclei using a 1 cm2 optical grid performed in 5, 40× fields. The mean Ki-67LI and Ki-67C were 56.4% (SD: 38.7) and 27.2 (SD: 12.9) and medians were 51% (range, 8.2–55.2) and 26 (range, 5.5–148), respectively. Using a cut-off of 56% and 9, respectively, Kaplan-Meier survival curves showed an association of overall survival with Ki-67LI and MC. In addition to clinical stage, Ki-67LI maintained its prognostic value on multivariate analysis, supporting the role of Ki-67LI as an independent prognostic parameter. Based on these results, we propose a diagnostically applicable cut-off value of 56% for Ki-67LI as a prognostic parameter for canine splenic hemangiosarcoma. [ABSTRACT FROM AUTHOR]

Abstract This study examined to evaluate the predictive value of a nomogram with Ki-67 in overall and disease-free survival in glioma patients, a total of 76 patients diagnosed with glioma by pathology in Tengzhou Central People’s Hospital were enrolled. The baseline data and follow ups were retrospectively collected from medical records. The associations between Ki-67 and survival status were examined using log-rank test, univariate and multivariate Cox proportional hazard regression models. Calibrations were performed to validate the established nomograms. Ki-67 negative group showed of a longer OS survival time and a longer PFS survival time with log-rank test (x2 = 16.101, P

Background: Neoadjuvant chemotherapy (NACT) affects the tumor protein marker’s expression and status. Changes in the expression of biomarkers during NACT may influence the clinical decision of adjuvant molecular and hormonal therapy. Hence, re-evaluation of receptor status has to be done after NACT to give a specific adjuvant therapy for patient benefit. Aims and Objectives: The aim of this study was to study the status of hormone receptors (HRs) – estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (Her-2/Neu), and Ki-67 in patients with locally advanced breast cancer (LABC) in both core needle biopsies and post-mastectomy specimens after administering neoadjuvant chemotherapy. Materials and Methods: The present study was conducted in the Department of Pathology in collaboration with the Department of Surgery, Pt B D Sharma PGIMS, Rohtak, for a period of 1 year. The study comprised 52 patients with LABC who received neoadjuvant chemotherapy and 20 control cases who did not receive neoadjuvant chemotherapy. Each case comprised two specimens: Trucut biopsy and a mastectomy specimen. Results: ER changed from positive to negative in 15.4% of the cases and from negative to positive in 1.9% of the cases. The overall change in ER was statistically significant (P=0.020). For PR, 9.6% of the cases changed from positive to negative while none of the cases showed change from negative to positive. The overall change in PR was statistically significant (P=0.025). For HER2/Neu, 19.2% of the cases changed from positive to negative, and 11.5% of the cases changed from negative to positive. The overall change in HER2/Neu was not statistically significant (P=0.317). For Ki-67, 30% of patients changed from positive to negative while 11.5% of patients changed from negative to positive. The overall change in Ki-67 was statistically significant (P=0.024). Conclusion: There was discordance in the HR status and proliferation marker after NACT in patients with breast cancer. The administration of NACT might be the main reason for the change in receptor status thus understanding the chemotherapy-induced biological conversion in the tumor cell behavior is strategically important in planning adjuvant endocrine therapy and for disease follow-up.

Today, diabetes mellitus (DM) represents a problem on which the attention of endocrinologists, general practitioners, and dentists is focused. Early pathological changes, which manifest themselves in the oral cavity, determine the relevance and social significance of this pathology, because dentists are usually the first to diagnose disorders of carbohydrate metabolism based on the results of the analysis of specific complaints and typical clinical symptoms of damage to the mucous membrane and periodontal tissues. The aim of the work is to find out the pathogenetic characteristics of the reparative component of the post-extraction alveolar socket depending on the time after tooth extraction in experimental diabetes. Materials and methods. In total, 120 sexually mature (age 8–10 months) male Wistar rats, divided into 8 groups of 15 animals each, were used for research. Complex immunohistological, radiographic and biochemical studies were used for the purpose of detailed analysis of the features of the course and mechanisms of development of complications after tooth extraction against the background of DM. In order to assess the state of the innate link of local immunity, the specifics of the course of repair processes at different times of the post-extraction period, the levels of cell proliferation (by expression of Ki-67) and the concentration and content of CD68-positive macrophages in the mucous membrane were determined immunohistochemically. In order to determine the state of the bone tissue of the dental and jaw apparatus and the levels of mineralization of the hard tissues of the molars in the animals of the experimental groups, radiovisiographic images of the right half-mandible were analyzed with determination of the radiographic density. Results. Analysis of proliferative-reparative relationships showed almost no macrophages and very low proliferative activity in the intact periodontium, on the other hand, in DM, initial significant diffuse infiltration by CD68-immunopositive cells with high levels of Ki-67 expression was found. Analysis of X-ray images of the half-mandible revealed that induced DM in rats, even without prior surgical intervention, led to the intensification of resorption processes in bone tissue, which was evidenced by a decrease in radiographic density in the root region of the 1st molar and intraalveolar bone membranes of all three lower molars. Conclusions. In the intact periodontium, there are almost no CD68-immunopositive macrophages and very low proliferation activity in the periodontal soft tissues. In experimental diabetes, on the contrary, initial significant diffuse infiltration by CD68-immunopositive macrophages with high proliferative activity of most fibroblasts is determined. Induced diabetes in rats, even without prior surgical intervention, leads to increased resorption processes in the bone tissue of the mandible and long-term prolongation of the inflammatory process after tooth extraction.

Abstract Objective To assess whether diffusion and perfusion MRI derived parameters could non-invasively predict PD-L1 and Ki-67 status in primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL). Methods We retrospectively analyzed DWI, DSC-PWI, and morphological MRI (mMRI) in 88 patients with PCNS-DLBCL. The mMRI features were compared using chi-square tests or Fisher exact test. Minimum ADC (ADCmin), mean ADC(ADCmean), relative minimum ADC (rADCmin), relative mean ADC (rADCmean), and relative maximum CBV (rCBVmax) values were compared in PCNS-DLBCL with different molecular status by using the Mann-Whitney U test. The diagnostic performances were evaluated by receiver operating characteristic curves. Results PCNS-DLBCL with high PD-L1 expression demonstrated a significantly higher ADCmin value than those with low PD-L1. The ADCmean and rADCmean values were significantly lower in PCNS-DLBCL with high Ki-67 status compared with those in low Ki-67 status. Other ADC, CBV parameters, and mMRI features did not show any association with these molecular statuses The diagnostic efficacy of ADC values in assessing PD-L1 and Ki-67 status was relatively low, with area under the curves (AUCs) values less than 0.7. Conclusions DWI-derived ADC values can provide some relevant information about PD-L1 and Ki-67 status in PCNS-DLBCL, but may not be sufficient to predict their expression due to the rather low diagnostic performance.

Abstract Background Myxofibrosarcoma is a myxoid soft tissue sarcoma showing T2 high intensity on magnetic resonance imaging. However, myxofibrosarcoma is a heterogeneous sarcoma with both myxoid and cellular portions. Magnetic resonance imaging findings were obtained MRI findings for comparison with histological and Ki-67 immunohistochemical features, in different portions of one myxofibrosarcoma. Case presentation Magnetic resonance imaging observations were compared with gross pathological and microscopic findings of a myxofibrosarcoma from a 50-year-old Japanese female. The Ki-67 labeling indices of different portions of the tumor, that is, the myxoid, cellular, and histologically confirmed infiltrative margin portions (pathological tail sign), were compared. The T2 low intensity area was more cellular than the T2 high intensity area, while the cellular portion had a significantly higher Ki-67 index than the myxoid portion (p = 0.0313). The portions with the pathological tail sign had a significantly higher Ki-67 labeling index than those without this sign (p = 0.0313). Conclusions More cellular portions of a myxofibrosarcoma correspond to more areas of the tumor showing aggressive features. Furthermore, our data also support the hypothesis of high aggressiveness being associated with the pathological tail sign in myxofibrosarcoma. To our knowledge, this is the first case report to describe comparisons among the imaging findings, histological features, and Ki-67 immunohistochemistry results for different portions of one myxofibrosarcoma.

Abstract Background Vascular invasion (VI) is closely related to the metastasis, recurrence, prognosis, and treatment of gastric cancer. Currently, predicting VI preoperatively using traditional clinical examinations alone remains challenging. This study aims to explore the value of radiomics analysis based on preoperative enhanced CT images in predicting VI in gastric cancer. Methods We retrospectively analyzed 194 patients with gastric adenocarcinoma who underwent enhanced CT examination. Based on pathology analysis, patients were divided into the VI group (n = 43) and the non-VI group (n = 151). Radiomics features were extracted from arterial phase (AP) and portal venous phase (PP) CT images. The radiomics score (Rad-score) was then calculated. Prediction models based on image features, clinical factors, and a combination of both were constructed. The diagnostic efficiency and clinical usefulness of the models were evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Results The combined prediction model included the Rad-score of AP, the Rad-score of PP, Ki-67, and Lauren classification. In the training group, the area under the curve (AUC) of the combined prediction model was 0.83 (95% CI 0.76–0.89), with a sensitivity of 64.52% and a specificity of 92.45%. In the validation group, the AUC was 0.80 (95% CI 0.67–0.89), with a sensitivity of 66.67% and a specificity of 88.89%. DCA indicated that the combined prediction model might have a greater net clinical benefit than the clinical model alone. Conclusion The integrated models, incorporating enhanced CT radiomics features, Ki-67, and clinical factors, demonstrate significant predictive capability for VI. Moreover, the radiomics model has the potential to optimize personalized clinical treatment selection and patient prognosis assessment.

Abstract Objectives To develop and validate a radiomics nomogram combining radiomics features and clinical factors for preoperative evaluation of Ki-67 expression status and prognostic prediction in clear cell renal cell carcinoma (ccRCC). Methods Two medical centers of 185 ccRCC patients were included, and each of them formed a training group (n = 130) and a validation group (n = 55). The independent predictor of Ki-67 expression status was identified by univariate and multivariate regression, and radiomics features were extracted from the preoperative CT images. The maximum relevance minimum redundancy (mRMR) and the least absolute shrinkage and selection operator algorithm (LASSO) were used to identify the radiomics features that were most relevant for high Ki-67 expression. Subsequently, clinical model, radiomics signature (RS), and radiomics nomogram were established. The performance for prediction of Ki-67 expression status was validated using area under curve (AUC), calibration curve, Delong test, decision curve analysis (DCA). Prognostic prediction was assessed by survival curve and concordance index (C-index). Results Tumour size was the only independent predictor of Ki-67 expression status. Five radiomics features were finally identified to construct the RS (AUC: training group, 0.821; validation group, 0.799). The radiomics nomogram achieved a higher AUC (training group, 0.841; validation group, 0.814) and clinical net benefit. Besides, the radiomics nomogram provided a highest C-index (training group, 0.841; validation group, 0.820) in predicting prognosis for ccRCC patients. Conclusions The radiomics nomogram can accurately predict the Ki-67 expression status and exhibit a great capacity for prognostic prediction in patients with ccRCC and may provide value for tailoring personalized treatment strategies and facilitating comprehensive clinical monitoring for ccRCC patients.

Adenoid cystic carcinoma is a rare malignant tumor that primarily occurs in the salivary glands. There are few reports of sublingual gland adenoid cystic carcinoma with lung metastases on which 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) was performed. We report the case of a 57-year-old Japanese woman with an adenoid cystic carcinoma of the sublingual gland with lung metastases in whom the FDG uptake of the lung metastasis was low despite high FDG uptake in the primary lesion. The pathological examination revealed that solid components were more visible and the Ki-67 index was more positive in the primary lesion compared to the metastatic lesion. We speculate that differences in tumor growth ability might have resulted in the differences in FDG uptake. This case demonstrates that significant differences might occur in the FDG uptake between primary and metastatic tumors.

Background and purpose: One of the most important mechanisms of tissue regeneration is the high functional activity of cells, including proliferation. Currently, there are practically no effective skin cell activators on the pharmaceutical market. The purpose of this work was to demonstrate the stimulating effect of spiroconjugated 1,2,3-triazolo[5,1-b]1,3,4-thiadiazine (STT) on the functional activity of fibroblasts. Experimental approach: STT containing ointment for dermal application was made. To assess in vivo effect of the STT a linear wound model in rats was tested. A combination of histological techniques and mechanical testing was employed to estimate the stimulating effect of STT on the functional activity of fibroblasts. Findings/Results: The STT significantly increased the number of fibroblasts as well as the density and order of produced collagen fibers in the dermis during the wound healing process. As a result, a tissue was formed at the site of damage with the structure corresponding to normal skin. In addition, skin functions were restored, in particular mechanically. Conclusion and implications: The results suggested the stimulating effect of the STT on fibroblast activity and demonstrated its potential for skin regeneration.

Abstract Background Immunohistochemistry (IHC) is widely used in the management of patients with cervical intraepithelial neoplasia (CIN) but still has many limitations in clinical practice. We analyzed the correlation of new biomarkers with the severity of CIN and follow-up outcomes in patients after conization to improve the management of patients with CIN. Methods IHC staining of Eag1 and p16/Ki-67 was performed on cervical tissue sections from 234 patients with suspected CIN2/3. After a series of follow-ups, including human papillomavirus (HPV) test and thinprep cytologic test (TCT) for 1–2 years, the outcomes were collected. IHC scores of biomarkers and follow-up results were used to analyze the correlation and assess the diagnostic efficiency of biomarkers. Results The IHC staining intensity of Eag1 and p16/Ki-67 was significantly different from that of the CIN1-3 groups (p

Objective: Neoadjuvant chemotherapy (NAC) in breast cancer (BC) is being considered for a broader range of cases, including locally advanced tumors and situations where downstaging could reduce extensive surgery. Several trials have explored predictive markers of pathological complete response (pCR). The role of Ki-67 as a predictor of pCR has been demonstrated in studies. However, the cut-off remains vague, given the lack of standardization of measurement methods. The aim of our study was to evaluate the predictive value of Ki-67 in response to NAC and to identify the cut-off values that exhibit the strongest correlation with best response. Materials and Methods: This retrospective study included 187 patients who had undergone surgery following NAC for BC at the CHU Souss Massa of Agadir between January 2020 and January 2023. Logistic regression was used to assess the correlation between Ki-67 and patients’ characteristics. Optimal Ki-67 cutoff was identified by receiver operating characteristic curve. Kaplan-Meier curves were used to assess disease-free survival (DFS), and survival comparisons were assessed with the log-rank test. Results: The median age was 51.8±10.7 years and 51.4% of tumors were smaller than 5 cm. Node invasion was found in 55.4%. Luminal B subtype was found in 49.7%, followed by human epidermal growth factor receptor-2 (HER-2)-positive in 27.4%, triple-negative in 14.3% and Luminal A in 8.6%. pCR occurred in 40% of patients overall. Subgroup analysis revealed a significant association between pCR and tumor size (p35% (p35% predicts a better pCR rate in response to NAC. However, this cutoff value remains controversial due to the absence of a standard method of measurement, with inter- and intra-observer variability. It would be necessary to validate this cutoff in other studies.

Objective To summarize the clinicopathological characteristics and prognostic factors of salivary duct carcinoma (SDC) patients. Methods This study was reviewed and approved by the Ethics Committee, and informed consent was obtained from the patients. The clinical data of 30 SDC patients who were admitted to the Fourth Hospital of Hebei Medical University from 2014 to 2022, including case records, pathological diagnoses, immunohistochemical indicators, treatment methods, follow-up data, and other data, were retrospectively analyzed. SPSS 26.0 software was used to process the data and construct relevant curves. The chi-square test was used to analyze the correlation between different immunohistochemical indices and the recurrence and metastasis of SDC, and a single factor was used to analyze clinical prognostic factors. Results Among the 30 SDC patients, the male-to-female ratio was 5∶1, with a median age of 61.5 years. Approximately 60% of cases occurred in the parotid gland, whereas the remainder occurred in the submaxillary gland, sublingual gland, or minor salivary gland. Among them, 19 patients were androgen receptor-positive, 23 patients were human epidermal growth factor receptor-2 positive, and 26 patients were Ki-67 positive. Postoperative follow-up was 18-94 months, with a median follow-up of 37 months. There were 13 cases of recurrence and 14 cases of distant metastasis. The 5-year overall survival rate was only 31.2%. The long-term survival of patients who underwent postoperative radiotherapy and chemoradiotherapy was better than that of patients who underwent surgery alone (P= 0.027). T stage and lymph node invasion were associated with prognosis and survival (PP = 0.025). Conclusion Radical surgery combined with postoperative radiotherapy and chemoradiotherapy is helpful for improving long-term overall survival, and tumor T stage and lymph node metastasis may be the main factors affecting the prognosis of patients with SDC. Patients with Ki-67-positive cell counts ≥ 40% are prone to postoperative recurrence or metastasis.

Intravascular papillary endothelial hyperplasia (IPEH) is a benign lesion characterized by reactive proliferation of endothelial cells with papillary formations related to thrombosed blood vessels. IPEH in the oral region is relatively rare, and its clinical picture is not specific. Herein, we report the case of a patient with IPEH of the upper lip who had a favorable outcome. A man in his 40 s presented to our department with a nodule beneath the right upper labial mucosa. Magnetic resonance imaging showed a relatively well-defined mass. Based on the diagnosis of a benign tumor, a total excision with healthy margins was performed. Histopathological and immunohistochemical findings revealed a pure form of IPEH with a Ki-67 labeling index of 20%. No recurrence was observed 1 year postoperatively. Although IPEH in the oral region is relatively rare, and its clinical presentation is nonspecific, based on the clinical diagnosis of benign tumors, adequate excision with clear margins can reduce the risk of recurrence. As Ki-67 can be used to predict the biological behavior and risk of IPEH recurrence, careful follow-up considering the risk of recurrence suggested by the Ki-67 labeling index is needed. Thorough knowledge of IPEH is important for clinicians and pathologists to arrive at a correct diagnosis, which leads to appropriate treatment. [ABSTRACT FROM AUTHOR]

The reporting of lung neuroendocrine neoplasms (NENs) according to the 2021 World Health Organisation (WHO) is based on mitotic count per 2 mm2, necrosis assessment and a constellation of cytological and immunohistochemical details. Accordingly, typical carcinoid and atypical carcinoid are low‐ to intermediate‐grade neuroendocrine tumours (NETs), while large‐cell neuroendocrine carcinoma (NEC) and small‐cell lung carcinoma are high‐grade NECs. In small‐sized diagnostic material (cytology and biopsy), the noncommittal term of carcinoid tumour/NET not otherwise specified (NOS) and metastatic carcinoid NOS have been introduced with regard to primary and metastatic diagnostic settings, respectively. Ki‐67 antigen, a well‐known marker of cell proliferation, has been included in the WHO classification as a non‐essential but desirable criterion, especially to distinguish NETs from high‐grade NECs and to delineate the provisional category of carcinoid tumours/NETs with elevated mitotic counts (> 10 mitoses per mm2) and/or Ki‐67 proliferation index (≥ 30%). However, a wider use of this marker in the spectrum of lung NENs continues to be highly reported and debated, thus witnessing a never‐subsided attention. Therefore, the arguments for and against incorporating Ki‐67 in the classification and clinical practice of these neoplasms are discussed herein in detail. [ABSTRACT FROM AUTHOR]

Abstract Objective This study developed and validated a nomogram utilizing clinical and multi-slice spiral computed tomography (MSCT) features for the preoperative prediction of Ki-67 expression in stage IA lung adenocarcinoma. Additionally, we assessed the predictive accuracy of Ki-67 expression levels, as determined by our model, in estimating the prognosis of stage IA lung adenocarcinoma. Materials and methods We retrospectively analyzed data from 395 patients with pathologically confirmed stage IA lung adenocarcinoma. A total of 322 patients were divided into training and internal validation groups at a 6:4 ratio, whereas the remaining 73 patients composed the external validation group. According to the pathological results, the patients were classified into high and low Ki-67 labeling index (LI) groups. Clinical and CT features were subjected to statistical analysis. The training group was used to construct a predictive model through logistic regression and to formulate a nomogram. The nomogram’s predictive ability and goodness-of-fit were assessed. Internal and external validations were performed, and clinical utility was evaluated. Finally, the recurrence-free survival (RFS) rates were compared. Results In the training group, sex, age, tumor density type, tumor-lung interface, lobulation, spiculation, pleural indentation, and maximum nodule diameter differed significantly between patients with high and low Ki-67 LI. Multivariate logistic regression analysis revealed that sex, tumor density, and maximum nodule diameter were significantly associated with high Ki-67 expression in stage IA lung adenocarcinoma. The calibration curves closely resembled the standard curves, indicating the excellent discrimination and accuracy of the model. Decision curve analysis revealed favorable clinical utility. Patients with a nomogram-predicted high Ki-67 LI exhibited worse RFS. Conclusion The nomogram utilizing clinical and CT features for the preoperative prediction of Ki-67 expression in stage IA lung adenocarcinoma demonstrated excellent performance, clinical utility, and prognostic significance, suggesting that this nomogram is a noninvasive personalized approach for the preoperative prediction of Ki-67 expression.

Abstract Background Current diagnostic criteria of adrenocortical neoplasms are mostly based on morphology. The utility of immunohistochemistry (IHC) and histochemistry is limited. Materials and methods To evaluate the diagnostic and prognostic utility of clinicopathological features, morphology, ancillary biomarkers, and reticular histochemistry in adrenocortical neoplasms. We examined 28 adrenocortical carcinomas (ACCs) and 50 adrenocortical adenomas (ACAs) obtained from pathology archives. Clinical data were retrieved from medical records. Two pathologists independently assessed hematoxylin and eosin-stained slides, employing modified Weiss criteria for all tumors and Lin-Weiss-Bisceglia criteria for oncocytic variants. Immunohistochemical markers (Calretinin, alpha-inhibin, MelanA, SF-1, Ki-67, PHH3, IGF-2, β-catenin, P53, CYP11B1, CYP11B2, MLH1, MSH2, MSH6, PMS2, EPCAM) and Gomori’s Silver histochemistry were applied. Statistical analysis utilized SPSS Statistics 26. Results ACCs exhibited larger tumor sizes (P

Objective: Tumor cell malignancy is indicated by histopathological differentiation and cell proliferation. Ki-67, an indicator of cellular proliferation, has been used for tumor grading and classification in breast cancer and neuroendocrine tumors. However, its prognostic significance in pancreatic ductal adenocarcinoma (PDAC) remains uncertain. Methods: Patients who underwent radical pancreatectomy for PDAC were retrospectively enrolled, and relevant prognostic factors were examined. Grade of malignancy (GOM), a novel index based on histopathological differentiation and Ki-67, is proposed, and its clinical significance was evaluated. Results: The optimal threshold for Ki-67 was determined to be 30%. Patients with a Ki-67 expression level > 30% rather than ≤ 30% had significantly shorter 5-year overall survival (OS) and recurrence-free survival (RFS). In multivariate analysis, both histopathological differentiation and Ki-67 were identified as independent prognostic factors for OS and RFS. The GOM was used to independently stratify OS and RFS into 3 tiers, regardless of TNM stage and other established prognostic factors. The tumor-node-metastasis-GOM stage was used to stratify survival into 5 distinct tiers, and surpassed the predictive performance of TNM stage for OS and RFS. Conclusions: Ki-67 is a valuable prognostic indicator for PDAC. Inclusion of the GOM in the TNM staging system may potentially enhance prognostic accuracy for PDAC.

Squamous cell carcinoma (SCC) stands as the second most prevalent skin cancer in dogs, primarily attributed to UV radiation exposure. Affected areas typically include regions with sparse hair and pale or depigmented skin. The significance of spontaneous canine cutaneous SCC as a model for its human counterpart is underscored by its resemblance. This study assesses the expression of key markers—Epidermal Growth Factor Receptor (EGFR), Cyclooxygenase-2 (Cox-2), and Ki-67—in canine cutaneous SCC. Our objective is to investigate the association between their expression levels and classical clinicopathological parameters, unraveling the intricate relationships among these molecular markers. In our retrospective analysis of 37 cases, EGFR overexpression manifested in 43.2% of cases, while Cox-2 exhibited overexpression in 97.3%. The EGFR, Cox-2 overexpression, and Ki-67 proliferation indices, estimated through immunohistochemistry, displayed a significant association with the histological grade, but only EGFR labeling is associated with the presence of lymphovascular emboli. The Ki-67 labeling index expression exhibited an association with EGFR and Cox-2. These findings propose that EGFR, Cox-2, and Ki-67 hold promise as valuable markers in canine SCC. EGFR, Cox-2, and Ki-67 may serve as indicators of disease progression, offering insights into the malignancy of a lesion. The implications extend to the potential therapeutic targeting of EGFR and Cox-2 in managing canine SCC. Further exploration of these insights is warranted due to their translational relevance and the development of targeted interventions in the context of canine SCC.

Abstract Background The proliferation antigen Ki-67 has been widely used in clinical settings for cancer staging for many years, but investigations on its biological functions have lagged. Recently, Ki-67 has been shown to regulate both the composition of the chromosome periphery and chromosome behaviour in mitosis as well as to play a role in heterochromatin organisation and gene transcription. However, how the different roles for Ki-67 across the cell cycle are regulated and coordinated remain poorly understood. The progress towards understanding Ki-67 function have been limited by the tools available to deplete the protein, coupled to its abundance and fluctuation during the cell cycle. Results Here, we use a doxycycline-inducible E3 ligase together with an auxin-inducible degron tag to achieve a rapid, acute and homogeneous degradation of Ki-67 in HCT116 cells. This system, coupled with APEX2 proteomics and phospho-proteomics approaches, allows us to show that Ki-67 plays a role during DNA replication. In its absence, DNA replication is severely delayed, the replication machinery is unloaded, causing DNA damage that is not sensed by the canonical pathways and dependent on HUWE1 ligase. This leads to defects in replication and sister chromatids cohesion, but it also triggers an interferon response mediated by the cGAS/STING pathway in all the cell lines tested. Conclusions We unveil a new function of Ki-67 in DNA replication and genome maintenance that is independent of its previously known role in mitosis and gene regulation.

Non-malignant breast diseases (NMBD) may increase the risk of developing a malignant neoplasm. Therefore, it seems relevant to search for criteria for cell malignancy in NMBD. Aim of the study was to investigate the relationship between expression of proliferation and epithelial-mesenchymal transition (EMT) markers and histidine-rich glycoprotein (HRG) mRNA in breast diseases. Material and methods. In breast biopsy specimens of 37 patients with invasive carcinoma of a non-specific type (ICNT) and 17 patients with NMBD expression of proliferation markers (Ki-67, cyclin D1 (CCND1)) and EMT markers (E-cadherin (CDH1), type II collagen (CII) and β1-integrin (CD29)) was determined immunohistochemically. HRG mRNA expression was estimated using real time PCR. Results. HRG mRNA expression was detected in 91.9 % cases (34 of 37) in ICNT, 82.4 % (14 of 17) in NMBD and in the latter case was inversely related to the expression of CDH1, CD29 and Ki-67. A direct relationship has been established between the presence of Ki-67 and CCND1, CII, between CCND1 and CD29 in NMBD. In patients with ICNT, a direct correlation was found between the HRG mRNA expression and the presence of CII, and an inverse correlation between the number of cells containing CII and CD29. It was found that in ICNT and NMBD with the presence of HRG mRNA expression, the CDH1 expression is less than in its absence. Conclusions. Indicators of HRG mRNA expression in NMBD, combined with the assessment of proliferation and EMT markers, can be useful in developing criteria for cell malignancy in benign breast diseases.