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Background/Objectives: Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) is an antagonist of transforming growth factor (TGF)-β type 1 signaling. BAMBI functions as an anti-fibrotic protein and exerts pro- as well as anti-cancerogenic activities. Our study aimed to correlate hepatocyte BAMBI protein levels in hepatocellular carcinoma (HCC) with T stage, lymph node invasion, vessel invasion, grading, tumor size and Union for International Cancer Control (UICC) stage, as well as with liver inflammation and fibrosis stages. Methods: Hepatocyte BAMBI protein expression was assessed by immunohistochemistry in HCC tissues of 320 patients and non-tumor tissues of 51 patients. Results: In the HCC tissues of the whole cohort and sex-specific analysis, BAMBI protein was not related to T stage, vessel invasion, lymph node invasion, histologic grade, UICC stage and tumor size. Accordingly, BAMBI was not associated with overall survival, recurrence-free and metastasis-free survival. BAMBI protein levels in tumor and non-tumor tissues were not related to inflammation and fibrosis grade. BAMBI protein levels in HCC tissues and non-tumor tissues from HCC patients, which were analyzed by immunoblot in a small cohort and by immunohistochemistry in the tissues of patients described above, were similar. Notably, BAMBI protein was low-abundant in HCC tissues of hepatitis C virus (HCV) compared to hepatitis B virus (HBV)-infected patients with comparable disease severity. Immunoblot analysis revealed reduced BAMBI protein in non-tumor tissues of patients with HCV in comparison to patients with HBV and normal human liver tissues. Conclusions: In summary, this analysis showed that hepatocyte BAMBI protein levels of patients with HCC are related to HCV infection rather than the severity of the underlying liver disease and cancer staging. [ABSTRACT FROM AUTHOR]

Simple Summary: Current clinical practice guidelines support additional locoregional surgery after local resection of early colorectal cancer when one or more of the following risk factors are present: poor differentiation grade, lymphovascular invasion, deep submucosal invasion, moderate or high tumor budding, and deep margin involvement. The absence of all these risk criteria selects a subgroup of patients with very good prognosis that can safely avoid additional surgery. However, lymph node metastases are only identified in 10–20% of patients who ultimately undergo additional surgery, so that 80–90% of the surgeries turn out to be unnecessary. In this investigation, we find that indicating additional surgery in early colorectal cancer only when either moderate or high tumor budding, poorly differentiated clusters, or lymphovascular invasion are present could reduce unnecessary surgeries by 40–45% without significantly increasing the proportion of patients with lymph node metastases who are not offered additional surgery. Background: The low positive predictive value for lymph node metastases (LNM) of common practice risk criteria (CPRC) in T1 colorectal carcinoma (CRC) leads to manyunnecessary additional surgeries following local resection. This study aimed to identify criteria that may improve on the CPRC. Methods: Logistic regression analysis was performed to determine the association of diverse variables with LNM or 'poor outcome' (LNM and/or distant metastases and/or recurrence) in a single center T1 CRC cohort. The diagnostic capacity of the set of variables obtained was compared with that of the CPRC. Results: The study comprised 161 cases. Poorly differentiated clusters (PDC) and tumor budding grade > 1 (TB > 1) were the only independent variables associated with LNM. The area under the curve (AUC) for these criteria was 0.808 (CI 95% 0.717–0.880) compared to 0.582 (CI 95% 0.479–0.680) for CPRC. TB > 1 and lymphovascular invasion (LVI) were independently associated with 'poor outcome', with an AUC of 0.801 (CI 95% 0.731–0.859), while the AUC for CPRC was 0.691 (CI 95% 0.603–0.752). TB > 1, combined either with PDC or LVI, would reduce false positives between 41.5% and 45% without significantly increasing false negatives. Conclusions: Indicating additional surgery in T1 CRC only when either TB > 1, PDC, or LVI are present could reduce unnecessary surgeries significantly. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) has consistently shown a global rise in incidence. p53 exerts regulatory function in signaling processes, with the p53 mutation accelerating the late stage of colorectal carcinogenesis. Programmed death ligand 1 (PD-L1) is an immune checkpoint regulator whose role in targeted therapy of CRCs needs to be evaluated. Beta-catenin plays a fundamental role in cell adhesion, with long-term effects on disease progression and survival. A detailed evaluation of all these factors is essential to tailoring new therapeutic approaches in advanced-stage cases. Aims and Objectives: To study the immunohistochemical (IHC) expression of p53, PD-L1, and beta-catenin in different histologic grades and stages of colorectal carcinomas. Materials and Methods: A total of 29 cases of segmental colectomy were included in the study population. Tumor sections were sent for IHC study of p53, PD-L1, and beta-catenin and interpreted as per standard protocol. Findings were tabulated against the histologic grade and stages of CRCs. Statistical analysis was done using SPSS 25.0 to test for statistical significance at P

Background: Colorectal cancer (CRC) has consistently shown a global rise in incidence. p53 exerts regulatory function in signaling processes, with the p53 mutation accelerating the late stage of colorectal carcinogenesis. Programmed death ligand 1 (PD-L1) is an immune checkpoint regulator whose role in targeted therapy of CRCs needs to be evaluated. Beta-catenin plays a fundamental role in cell adhesion, with long-term effects on disease progression and survival. A detailed evaluation of all these factors is essential to tailoring new therapeutic approaches in advanced-stage cases. Aims and Objectives: To study the immunohistochemical (IHC) expression of p53, PD-L1, and beta-catenin in different histologic grades and stages of colorectal carcinomas. Materials and Methods: A total of 29 cases of segmental colectomy were included in the study population. Tumor sections were sent for IHC study of p53, PD-L1, and beta-catenin and interpreted as per standard protocol. Findings were tabulated against the histologic grade and stages of CRCs. Statistical analysis was done using SPSS 25.0 to test for statistical significance at P<0.05. Results: The study population predominantly consisted of males (66%), mainly in the age group of 46-60 years. p53 was significantly more expressed in left colonic tumors. PD-L1 expression was also significantly associated with histologic grade and nodal metastasis. High beta-catenin expression was seen in well-differentiated adenocarcinomas and lower T and N-stage disease. Positive p53 also correlated with positive PD-L1 expression. However, expression of p53 was also high in tumors with low beta-catenin expression. Conclusion: p53, PD-L1, and beta-catenin may have a role in prognostication and predicting long-term survival outcomes in CRC cases. These may also act as potential therapeutic targets with a more detailed evaluation and a larger sample size of CRC cases. [ABSTRACT FROM AUTHOR]

Background/Objectives: Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) is an antagonist of transforming growth factor (TGF)-β type 1 signaling. BAMBI functions as an anti-fibrotic protein and exerts pro- as well as anti-cancerogenic activities. Our study aimed to correlate hepatocyte BAMBI protein levels in hepatocellular carcinoma (HCC) with T stage, lymph node invasion, vessel invasion, grading, tumor size and Union for International Cancer Control (UICC) stage, as well as with liver inflammation and fibrosis stages. Methods: Hepatocyte BAMBI protein expression was assessed by immunohistochemistry in HCC tissues of 320 patients and non-tumor tissues of 51 patients. Results: In the HCC tissues of the whole cohort and sex-specific analysis, BAMBI protein was not related to T stage, vessel invasion, lymph node invasion, histologic grade, UICC stage and tumor size. Accordingly, BAMBI was not associated with overall survival, recurrence-free and metastasis-free survival. BAMBI protein levels in tumor and non-tumor tissues were not related to inflammation and fibrosis grade. BAMBI protein levels in HCC tissues and non-tumor tissues from HCC patients, which were analyzed by immunoblot in a small cohort and by immunohistochemistry in the tissues of patients described above, were similar. Notably, BAMBI protein was low-abundant in HCC tissues of hepatitis C virus (HCV) compared to hepatitis B virus (HBV)-infected patients with comparable disease severity. Immunoblot analysis revealed reduced BAMBI protein in non-tumor tissues of patients with HCV in comparison to patients with HBV and normal human liver tissues. Conclusions: In summary, this analysis showed that hepatocyte BAMBI protein levels of patients with HCC are related to HCV infection rather than the severity of the underlying liver disease and cancer staging.

Objective: The aim of this study is to analyze the differences in independent prognostic factors of cancer-specific survival (CSS) and overall survival (OS) in patients with different grades of histologic differentiation of colorectal cancer (CRC) who received preoperative neoadjuvant chemotherapy (NAC) and to establish a nomogram for predicting postoperative survival based on moderately differentiated CRC. Methods: We analyzed CRC patients from the SEER database who received NAC before operation between 2010 and 2015. The Kaplan-Meier curves were drawn to describe the differences in CSS and OS of CRC patients with different histologic grades of differentiation. Cox regression analysis was used to determine the independent prognostic factors. Nomograms were established to predict CSS and OS at 3 and 5 years by integrating independent prognostic factors. The calibration curve, receiver operating characteristic (ROC) curve, and C-index were used to verify nomograms. Results: A total of 6481 patients with CRC who received preoperative NAC were included in this study. Patients with different grades of histologic differentiation had significant differences in CSS and OS (P < 0.001), and the independent prognostic factors of different grades of histologic differentiation showed heterogeneity. In patients with moderately differentiated grade CRC, the independent prognostic factors for CSS and OS were age, race, marital status, serum carcinoembryonic antigen (CEA) level before treatment, site of primary tumor, histologic type, pT stage, pN stage, liver metastasis, and lung metastasis. Nomograms were established based on the independent prognostic factors of moderately differentiated grade CRC, and its calibration curves, area under the curve (AUC), and C-index showed good prediction accuracy. Conclusions: The independent prognostic factors of CSS and OS are different in patients with different grades of histologic differentiation of CRC who received NAC before the operation. Nomograms can be used to predict the survival of patients with moderately differentiated grade CRC who received preoperative NAC and to assist clinicians in making clinical decisions. [ABSTRACT FROM AUTHOR]

We explored the added value of a radiomic strategy based on quantitative transverse relaxation (T2) mapping and conventional magnetic resonance imaging (MRI) to evaluate the histologic grade of bladder cancer (BCa) preoperatively. Patients who were suspected of BCa underwent pelvic MRI (including T2 mapping and diffusion-weighted imaging (DWI) before any treatment. All patients with histological-proved urothelial BCa were included. We constructed different prediction models using the mean signal values and radiomic features from both T2 mapping and apparent diffusion coefficient (ADC) maps. The diagnostic performance of each model or parameter was assessed using receiver operating characteristic curves. In total, 92 patients were finally included (training cohort, n = 64; testing cohort, n = 28); among these, 71 had high-grade BCa. In the testing cohort, the T2-mapping radiomic model achieved the highest prediction performance (area under the curve (AUC), 0.87; 95% confidence interval (CI), 0.73–1.0) compared with the ADC radiomic model (AUC, 0.77; 95%CI, 0.56–0.97), and the joint radiomic model of 0.78 (95%CI, 0.61–0.96). Our results demonstrated that radiomic mapping could provide more information than direct evaluation of T2 and ADC values in differentiating histological grades of BCa. Additionally, among the radiomic models, the T2-mapping radiomic model outperformed the ADC and joint radiomic models. [ABSTRACT FROM AUTHOR]

Nottingham histological grade (NHG) 2 breast cancer has an intermediate risk of recurrence, which is not informative for therapeutic decision-making. We sought to develop and independently validate an MRI-based radiomics signature (Rad-Grade) to improve prognostic re-stratification of NHG 2 tumors. Nine hundred-eight subjects with invasive breast cancer and preoperative MRI scans were retrospectively obtained. The NHG 1 and 3 tumors were randomly split into training and independent test cohort, with the NHG 2 as the prognostic validation set. From MRI image features, a radiomics-based signature predictive of the histological grade was built by use of the LASSO logistic regression algorithm. The model was developed for identifying NHG 1 and 3 radiological patterns, followed with re-stratification of NHG 2 tumors into Rad-Grade (RG)2-low (NHG 1-like) and RG2-high (NHG 3-like) subtypes using the learned patterns, and the prognostic value was assessed in terms of recurrence-free survival (RFS). The Rad-Grade showed independent prognostic value for re-stratification of NHG 2 tumors, where RG2-high had an increased risk for recurrence (HR 2.20, 1.10–4.40, p = 0.026) compared with RG2-low after adjusting for established risk factors. RG2-low shared similar phenotypic characteristics and RFS outcomes with NHG 1, and RG2-high with NHG 3, revealing that the model captures radiomic features in NHG 2 that are associated with different aggressiveness. The prognostic value of Rad-Grade was further validated in the NHG2 ER+ (HR 2.53, 1.13–5.56, p = 0.023) and NHG 2 ER+LN– (HR 5.72, 1.24–26.44, p = 0.025) subgroups, and in specific treatment contexts. The radiomics-based re-stratification of NHG 2 tumors offers a cost-effective promising alternative to gene expression profiling for tumor grading and thus may improve clinical decisions. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate whether ultra-high-field dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the breast at 7T using quantitative pharmacokinetic (PK) analysis can differentiate between benign and malignant breast tumors for improved breast cancer diagnosis and to predict molecular subtypes, histologic grade, and proliferation rate in breast cancer. In this prospective study, 37 patients with 43 lesions suspicious on mammography or ultrasound underwent bilateral DCE-MRI of the breast at 7T. PK parameters (KTrans, kep, Ve) were evaluated with two region of interest (ROI) approaches (2D whole-tumor ROI or 2D 10 mm standardized ROI) manually drawn by two readers (senior reader, R1, and R2) independently. Histopathology served as the reference standard. PK parameters differentiated benign and malignant lesions (n = 16, 27, respectively) with good accuracy (AUCs = 0.655-0.762). The addition of quantitative PK analysis to subjective BI-RADS classification improved breast cancer detection from 88.4% to 97.7% for R1 and 86.04% to 97.67% for R2. Different ROI approaches did not influence diagnostic accuracy for both readers. Except for KTrans for whole-tumor ROI for R2, none of the PK parameters were valuable to predict molecular subtypes, histologic grade, or proliferation rate in breast cancer. In conclusion, PK-enhanced BI-RADS is promising for the noninvasive differentiation of benign and malignant breast tumors.

Abstract Background Accurate pathological diagnosis of invasion depth and histologic grade is key for clinical management in patients with bladder cancer (BCa), but it is labour-intensive, experience-dependent and subject to interobserver variability. Here, we aimed to develop a pathological artificial intelligence diagnostic model (PAIDM) for BCa diagnosis. Methods A total of 854 whole slide images (WSIs) from 692 patients were included and divided into training and validation sets. The PAIDM was developed using the training set based on the deep learning algorithm ScanNet, and the performance was verified at the patch level in validation set 1 and at the WSI level in validation set 2. An independent validation cohort (validation set 3) was employed to compare the PAIDM and pathologists. Model performance was evaluated using the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value and negative predictive value. Results The AUCs of the PAIDM were 0.878 (95% CI 0.875–0.881) at the patch level in validation set 1 and 0.870 (95% CI 0.805–0.923) at the WSI level in validation set 2. In comparing the PAIDM and pathologists, the PAIDM achieved an AUC of 0.847 (95% CI 0.779–0.905), which was non-inferior to the average diagnostic level of pathologists. There was high consistency between the model-predicted and manually annotated areas, improving the PAIDM’s interpretability. Conclusions We reported an artificial intelligence-based diagnostic model for BCa that performed well in identifying invasion depth and histologic grade. Importantly, the PAIDM performed admirably in patch-level recognition, with a promising application for transurethral resection specimens.

Abstract Background Recent studies have shown a lower likelihood of locoregional recurrences in patients with a low 21-gene recurrence score (RS). In this single-institution study, we investigated whether there are any associations between different cutoff values of 21-gene RS, histopathological factors, and outcome in patients with long-term follow-up. Methods The study included 61 patients who had early-stage (I-II) clinically node-negative hormone receptor-positive and HER2-negative breast cancer and were tested with the 21-gene RS assay between February 2010 and February 2013. Demographic, clinicopathological, treatment, and outcome characteristics were analyzed. Results The median age was 48 years (range, 29–72 years). Patients with high histologic grade (HG), Ki-67 ≥ 25%, or Ki-67 ≥ 30% were more likely to have intermediate/high RS (≥ 18). Based on the 21-gene RS assay, only 19 patients (31%) received adjuvant chemotherapy. At a median follow-up of 112 months, 3 patients developed locoregional recurrences (4.9%), which were treated with endocrine therapy alone. Among patients treated with endocrine treatment alone (n = 42), the following clinicopathological characteristics were not found to be significantly associated with 10-year locoregional recurrence free survival (LRRFS): age 11. However, patients with RS ≥ 16 had significantly poorer 10-year LRRFS compared to those with RS

Shihui Wang, Yi Wei, Zhouli Li, Jingya Xu, Yunfeng Zhou Department of Radiology, The First Affiliated Hospital of Wannan Medical College, Wuhu, People’s Republic of ChinaCorrespondence: Yunfeng Zhou, Department of Radiology, The First Affiliated Hospital of Wannan Medical College, Wuhu, People’s Republic of China, Tel +86 18110876440, Email zhouyunfeng808@163.comBackground: Histological grade is an important factor in the overall prognosis of patients with invasive breast cancer. Therefore, the non-invasive assessment of histological grade in breast cancer patients is an increasing concern for clinicians. We aimed to establish an MRI-based radiomics model for preoperative prediction of invasive breast cancer histological grade.Methods: We enrolled 901 patients with invasive breast cancer and pre-operative MRI. Patients were randomly divided into the training cohort (n=630) and validation cohort (n=271) with a ratio of 7:3. A radiomics signature was constructed by extracting radiomics features from MRI images and was developed according to multivariate logistic regression analysis. The diagnostic performance of the radiomics model was assessed using receiver operating characteristic (ROC) curve analysis.Results: Of the 901 patients, 618 (68.6%) were histological grade 1 or 2 while 283 (31.4%) were histological grade 3. The area under the ROC curve (AUC) of the radiomics model for the prediction of the histological grade was 0.761 (95% CI 0.728– 0.794) in the training cohort and 0.722 (95% CI 0.664– 0.777) in the validation cohort. The decision curve analysis (DCA) demonstrated the radiomics model’s clinical application value.Conclusion: This is a preliminary study suggesting that the development of an MRI-based radiomics model can predict the histological grade of invasive breast cancer.Keywords: breast cancer, histologic grade, magnetic resonance imaging, radiomics, signature

Abstract Background The histological differentiation grades of gastric cancer (GC) are closely related to treatment choices and prognostic evaluation. Radiomics from dual-energy spectral CT (DESCT) derived iodine-based material decomposition (IMD) images may have the potential to reflect histological grades. Methods A total of 103 patients with pathologically proven GC (low-grade in 40 patients and high-grade in 63 patients) who underwent preoperative DESCT were enrolled in our study. Radiomic features were extracted from conventional polychromatic (CP) images and IMD images, respectively. Three radiomic predictive models (model-CP, model-IMD, and model-CP–IMD) based on solely CP selected features, IMD selected features and CP coupled with IMD selected features were constructed. The clinicopathological data of the enrolled patients were analyzed. Then, we built a combined model (model-Combine) developed with CP–IMD and clinical features. The performance of these models was evaluated and compared. Results Model-CP–IMD achieved better AUC results than both model-CP and model-IMD in both cohorts. Model-Combine, which combined CP–IMD radiomic features, pT stage, and pN stage, yielded the highest AUC values of 0.910 and 0.912 in the training and testing cohorts, respectively. Model-CP–IMD and model-Combine outperformed model-CP according to decision curve analysis. Conclusion DESCT-based radiomics models showed reliable diagnostic performance in predicting GC histologic differentiation grade. The radiomic features extracted from IMD images showed great promise in terms of enhancing diagnostic performance.

In recent years, more foreign publications are devoted to the use of texture analysis or radiomics in solving certain diagnostic problems, including the diagnosis of hepatocellular cancer (HCC). This method of processing medical images allows for a comprehensive assessment of the structure of neoplasms by extracting a large number of quantitative features from medical images.The purpose of the study was to determine the role of texture analysis of CT and MR images in differential diagnosis and determination of the degree of differentiation of HCC based on a review and analysis of the results of publications.We searched for scientific publications in the PubMed information and analytical system for 2015–2021. by keywords: “HCC”, “texture analysis” (texture analysis), “radiomics”, “CT”, “MRI”, “grade”, “differential diagnosis”. After excluding reviews of publications and studying the full text of articles, 21 articles were selected for analysis.Despite the growing number of publications devoted to the successful use of textural analysis of CT and MR images, including non-invasive assessment of the histological grade of HCC and in the differential diagnosis of HCC with hypervascular neoplasms, metastases, regenerative and dysplastic nodes, the use of such type of analysis in routine practice is limited due to the lack of standardized methods for performing texture analysis, which leads to low reproducibility of the results. The parameters of image acquisition and methods of image preprocessing and segmentation affect the reproducibility of the obtained texture features. In addition, the presented studies were performed using different MR sequences and phases of contrast enhancement, as well as different software, which makes it difficult to compare the obtained data.The use of texture analysis certainly demonstrates promising results and requires further investigation to systematize and standardize the obtained data in order to develop an optimal diagnostic model for wide clinical use.

The chemoattractant protein chemerin is protective in experimental hepatocellular carcinoma (HCC), and high expression in HCC tissues of Asian patients was related to a favorable prognosis. Studies from Asia found reduced expression of chemerin in HCC compared to para-tumor tissues while our previous analysis observed the opposite. Aim of this study was to correlate chemerin expression in HCC tissues with disease severity of European patients Hepatocyte chemerin protein expression was assessed by immunohistochemistry in HCC tissue of 383 patients, and was low in 24%, moderate in 49% and high in 27%. High chemerin protein in the HCC tissues was related to the T stage, vessel invasion, histologic grade, Union for International Cancer Control (UICC) stage and tumor size. Chemokine-like receptor 1 (CMKLR1) is a functional chemerin receptor. CMKLR1 protein in hepatocytes was low expressed in HCC tissues of 36%, moderate in tissues of 32% and high in 32% of the HCCs. Tumor CMKLR1 was associated with the T stage, vessel invasion, histologic grade and UICC stage. Notably, sex-specific analysis revealed that associations of chemerin and CMKLR1 expression with HCC progression were significant in males but not in females. The tumor chemerin and CMKLR1 protein expression were not related to steatosis, inflammation and fibrosis grades. In summary, chemerin as well as CMKLR1 protein were related to disease severity of European HCC patients, and this was significant in males. This observation is in contrast to Asian patients where higher chemerin in the tumors was protective. Current analysis provides evidence for ethnicity and sex-related differences of tumor expressed chemerin and HCC severity. [ABSTRACT FROM AUTHOR]

Although imaging is central in the initial staging of patients with soft tissue sarcomas (STS), it remains underused and few radiological features are currently used in practice for prognostication and to help guide the best therapeutic strategy. Yet, several prognostic qualitative and quantitative characteristics from magnetic resonance imaging (MRI) and positron emission tomography (PET) have been identified over these last decades. After an overview of the current validated prognostic features based on baseline imaging and their integration into prognostic tools, such as nomograms used by clinicians, the aim of this review is to summarize more complex and innovative MRI, PET, and radiomics features, and to highlight their role to predict indirectly (through histologic grade) or directly the patients' outcomes. [ABSTRACT FROM AUTHOR]

Estrogen receptor‐positive and human epidermal growth factor receptor 2‐negative (ER+HER2−) breast cancer accounts for ~ 60–70% of all cases of invasive breast carcinoma. High‐grade ER+HER2− tumors respond poorly to endocrine therapy. In this study, we systematically analyzed clinical and multi‐omics data to find potential strategies for personalized therapy of patients with high‐grade ER+HER2− disease. Six different cohorts were analyzed, for which multi‐omics data were available. Grade III ER+HER2− cases harbored higher proportions of large tumor size (> 5 cm), lymph node metastasis, chemotherapy use, and luminal B subtypes defined by PAM50, as compared with grade I/II tumors. DNA methylation (HM450) data and methylation‐specific PCR indicated that the cg18629132 locus in the MKI67 promoter was hypermethylated in grade I/II cases and normal tissue, but hypomethylated in grade III cases or triple‐negative breast cancer, resulting in higher expression of MKI67. Mutations in ESR1 and TP53 were detected in post‐endocrine treatment metastatic samples at a higher rate than in treatment‐naive tumors in grade III cases. We identified 42 and 20 focal copy number events in nonmetastatic and metastatic high‐grade ER+HER2− cases, respectively, with either MYC or MDM2 amplification representing an independent prognostic event in grade III cases. Transcriptional profiling within grade III tumors highlighted ER signaling downregulation and upregulation of immune‐related pathways in non‐luminal‐like tumors defined by PAM50. Recursive partitioning analysis was employed to construct a decision tree of an endocrine‐resistant subgroup (GATA3‐negative and AGR‐negative) of two genes that was validated by immunohistochemistry in a Chinese cohort. All together, these data suggest that grade III ER+HER2− tumors have distinct clinical and molecular characteristics compared with low‐grade tumors, particularly in cases with non‐luminal‐like biology. Due to the dismal prognosis in this group, clinical trials are warranted to test the efficacy of potential novel therapies.

Background: Accurate pathological diagnosis of invasion depth and histologic grade is key for clinical management in patients with bladder cancer (BCa), but it is labour-intensive, experience-dependent and subject to interobserver variability. Here, we aimed to develop a pathological artificial intelligence diagnostic model (PAIDM) for BCa diagnosis. Methods: A total of 854 whole slide images (WSIs) from 692 patients were included and divided into training and validation sets. The PAIDM was developed using the training set based on the deep learning algorithm ScanNet, and the performance was verified at the patch level in validation set 1 and at the WSI level in validation set 2. An independent validation cohort (validation set 3) was employed to compare the PAIDM and pathologists. Model performance was evaluated using the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value and negative predictive value. Results: The AUCs of the PAIDM were 0.878 (95% CI 0.875–0.881) at the patch level in validation set 1 and 0.870 (95% CI 0.805–0.923) at the WSI level in validation set 2. In comparing the PAIDM and pathologists, the PAIDM achieved an AUC of 0.847 (95% CI 0.779–0.905), which was non-inferior to the average diagnostic level of pathologists. There was high consistency between the model-predicted and manually annotated areas, improving the PAIDM's interpretability. Conclusions: We reported an artificial intelligence-based diagnostic model for BCa that performed well in identifying invasion depth and histologic grade. Importantly, the PAIDM performed admirably in patch-level recognition, with a promising application for transurethral resection specimens. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown a lower likelihood of locoregional recurrences in patients with a low 21-gene recurrence score (RS). In this single-institution study, we investigated whether there are any associations between different cutoff values of 21-gene RS, histopathological factors, and outcome in patients with long-term follow-up.Methods: The study included 61 patients who had early-stage (I-II) clinically node-negative hormone receptor-positive and HER2-negative breast cancer and were tested with the 21-gene RS assay between February 2010 and February 2013. Demographic, clinicopathological, treatment, and outcome characteristics were analyzed.Results: The median age was 48 years (range, 29-72 years). Patients with high histologic grade (HG), Ki-67 ≥ 25%, or Ki-67 ≥ 30% were more likely to have intermediate/high RS (≥ 18). Based on the 21-gene RS assay, only 19 patients (31%) received adjuvant chemotherapy. At a median follow-up of 112 months, 3 patients developed locoregional recurrences (4.9%), which were treated with endocrine therapy alone. Among patients treated with endocrine treatment alone (n = 42), the following clinicopathological characteristics were not found to be significantly associated with 10-year locoregional recurrence free survival (LRRFS): age < 40 years, age < 50 years, high histological or nuclear grade, high Ki-67-scores (≥ 15%, ≥ 20%, ≥ 25%, ≥ 30%), presence of lymphovascular invasion, luminal-A type, multifocality, lymph node positivity, tumor size more than 2 cm, RS ≥ 18, and RS > 11. However, patients with RS ≥ 16 had significantly poorer 10-year LRRFS compared to those with RS < 16 (75% vs. 100%, respectively; p = 0.039).Conclusions: The results suggest that patients with clinically node-negative disease and RS ≥ 16 are more likely to benefit from adjuvant chemotherapies. However, those with RS < 16 have an excellent outcome and local control in long-term follow-up with endocrine treatment alone. [ABSTRACT FROM AUTHOR]

Background: The histological differentiation grades of gastric cancer (GC) are closely related to treatment choices and prognostic evaluation. Radiomics from dual-energy spectral CT (DESCT) derived iodine-based material decomposition (IMD) images may have the potential to reflect histological grades. Methods: A total of 103 patients with pathologically proven GC (low-grade in 40 patients and high-grade in 63 patients) who underwent preoperative DESCT were enrolled in our study. Radiomic features were extracted from conventional polychromatic (CP) images and IMD images, respectively. Three radiomic predictive models (model-CP, model-IMD, and model-CP–IMD) based on solely CP selected features, IMD selected features and CP coupled with IMD selected features were constructed. The clinicopathological data of the enrolled patients were analyzed. Then, we built a combined model (model-Combine) developed with CP–IMD and clinical features. The performance of these models was evaluated and compared. Results: Model-CP–IMD achieved better AUC results than both model-CP and model-IMD in both cohorts. Model-Combine, which combined CP–IMD radiomic features, pT stage, and pN stage, yielded the highest AUC values of 0.910 and 0.912 in the training and testing cohorts, respectively. Model-CP–IMD and model-Combine outperformed model-CP according to decision curve analysis. Conclusion: DESCT-based radiomics models showed reliable diagnostic performance in predicting GC histologic differentiation grade. The radiomic features extracted from IMD images showed great promise in terms of enhancing diagnostic performance. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common malignant tumor in women. Some factors, including histological grade, vascular invasion, and metastasis, are known prognostic factors. Many studies have been performed to find more predictive factors such as urokinase plasminogen activator system markers. Here, we tried to evaluate the relationship between Urokinase-type plasminogen activator receptor expression and other histopathologic parameters. 62 malignant breast tumors were enrolled. UPAR immunohistochemistry staining was performed on paraffin blocks. We evaluated the relationship between UPAR expression and histopathologic factors, including tumor size, tumor type, histologic grade, lymph node status, lymphovascular and perineural invasions, and hormone receptors status (ER, PR, and HER2). The patient's mean age was 46.18±10.35 years. We found a positive relationship between UPAR expression and the presence of carcinoma insitu (P=0.027). A negative relationship was observed between UPAR expression and lymph node involvement (P=0.01), the number of involved lymph nodes (P=0.027), and also intensity and percentage of UPAR positivity in the case with lymph node involvement (P=0.005 and 0.029, respectively). UPAR expression is associated with lymph node metastasis which is one of the most important predictors of prognosis in breast cancer. So, it could be used as a favorable prognostic factor in breast cancer. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common malignant tumor in women. Some factors, including histological grade, vascular invasion, and metastasis, are known prognostic factors. Many studies have been performed to find more predictive factors such as urokinase plasminogen activator system markers. Here, we tried to evaluate the relationship between Urokinase-type plasminogen activator receptor expression and other histopathologic parameters. 62 malignant breast tumors were enrolled. UPAR immunohistochemistry staining was performed on paraffin blocks. We evaluated the relationship between UPAR expression and histopathologic factors, including tumor size, tumor type, histologic grade, lymph node status, lymphovascular and perineural invasions, and hormone receptors status (ER, PR, and HER2). The patient's mean age was 46.18±10.35 years. We found a positive relationship between UPAR expression and the presence of carcinoma insitu (P=0.027). A negative relationship was observed between UPAR expression and lymph node involvement (P=0.01), the number of involved lymph nodes (P=0.027), and also intensity and percentage of UPAR positivity in the case with lymph node involvement (P=0.005 and 0.029, respectively). UPAR expression is associated with lymph node metastasis which is one of the most important predictors of prognosis in breast cancer. So, it could be used as a favorable prognostic factor in breast cancer.

BackgroundBRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs).MethodsWe characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database.ResultsAmong BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10(-12)).ConclusionsOn the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.

The chemoattractant protein chemerin is protective in experimental hepatocellular carcinoma (HCC), and high expression in HCC tissues of Asian patients was related to a favorable prognosis. Studies from Asia found reduced expression of chemerin in HCC compared to para-tumor tissues while our previous analysis observed the opposite. Aim of this study was to correlate chemerin expression in HCC tissues with disease severity of European patients Hepatocyte chemerin protein expression was assessed by immunohistochemistry in HCC tissue of 383 patients, and was low in 24%, moderate in 49% and high in 27%. High chemerin protein in the HCC tissues was related to the T stage, vessel invasion, histologic grade, Union for International Cancer Control (UICC) stage and tumor size. Chemokine-like receptor 1 (CMKLR1) is a functional chemerin receptor. CMKLR1 protein in hepatocytes was low expressed in HCC tissues of 36%, moderate in tissues of 32% and high in 32% of the HCCs. Tumor CMKLR1 was associated with the T stage, vessel invasion, histologic grade and UICC stage. Notably, sex-specific analysis revealed that associations of chemerin and CMKLR1 expression with HCC progression were significant in males but not in females. The tumor chemerin and CMKLR1 protein expression were not related to steatosis, inflammation and fibrosis grades. In summary, chemerin as well as CMKLR1 protein were related to disease severity of European HCC patients, and this was significant in males. This observation is in contrast to Asian patients where higher chemerin in the tumors was protective. Current analysis provides evidence for ethnicity and sex-related differences of tumor expressed chemerin and HCC severity.

Oral squamous cell carcinoma (OSCC) occasionally occurs in young patients and is likely to be distinct from OSCC in older patients. In this retrospective study, we described the clinicopathologic features and outcome of 150 OSCCs that were diagnosed in patients 40-year-old or younger. Most patients (63%) were non-smokers. The most common site of the primary tumor was oral tongue (n = 131, 87%), followed by gingiva (n = 9), buccal mucosa (n = 8) and lip (n = 2). The median patients' age at presentation was 34 (range: 16–40). Seven patients (5%) had Fanconi anemia with the gingiva being the most common location (4/7, 57%). All OSCCs were of keratinizing type. All cases tested for high-risk HPV (n = 34) were negative. On univariate analysis, high tumor budding was associated with decreased overall survival (OS) and distant metastasis free survival (DMFS), pattern of invasion correlated with OS and tumors with high stromal tumor infiltrating lymphocytes (sTIL) were associated with improved locoregional recurrence free survival (LRFS). Compared with patients 31 to 40-year-old, OSCC in the younger group was associated with significant less alcohol consumption (p = 0.011) and decreased DSS (p = 0.003) and DMFS (p = 0.023). On multivariate analysis, younger age (30 years or younger) was an independent prognostic factor for worse OS and DSS, whereas histologic grade was an independent prognostic factor for DSS. In summary, most OSCC in young patients occurred in non-smokers and did not occur in association with Fanconi anemia. Independent prognostic factors included age at presentation (30 years or younger) for OS and DSS, and histologic grade for DSS. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to determine the oncological outcomes of mixed-grade tumors by comparing them with pure low-grade and high-grade tumors. Methods: We retrospectively reviewed the medical records of patients with primary non-muscle-invasive bladder cancer. Patients were categorized into three groups according to the histological grade of their tumors: low-grade, mixed-grade, and high-grade. Clinicopathological characteristics and oncological outcomes, such as recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS), were compared between the three groups. Results: A total of 369 patients (190 low, 40 mixed, and 139 high-grade) were included in our study, with a mean follow-up of 55.94±41.73 months. Patients with mixed-grade tumors had lower rates of pT1 stage diseases than those with high-grade tumors (42.5% vs. 64.0%, respectively) and higher rates than those with low-grade tumors (14.7% vs. 42.5%, respectively) (p=0.001). There was no significant difference in RFS between low-, mixed-, and high-grade tumor patients (p=0.887). Patients with mixed-grade tumors had worse PFS and CSS outcomes than those with low-grade tumors (199.84±23.22 vs. 214.94±15.92 for PFS and 202.07±19.86 vs. 233.61±9.84 for CSS, respectively) and better PFS and CSS outcomes than those with highgrade tumors (199.84±23.22 vs. 163.28±16.18 for PFS and 202.07±19.86 vs. 180.81±15.89 for CSS, respectively), although these comparisons were not statistically significant. Conclusions: Patients with mixed-grade tumors had worse PFS and CSS outcomes than patients with low-grade tumors and better PFS and CSS outcomes than patients with high-grade tumors, although these comparisons were not statistically significant. Our results should be verified by future studies. [ABSTRACT FROM AUTHOR]

PurposePrognostic factors affecting outcomes in pediatric spinal cord ependymomas are limited. We sought to investigate potential associations between extent of resection and histologic grade on progression-free survival (PFS) and overall survival (OS).MethodsA comprehensive literature search was performed to identify pediatric patients who underwent surgical resection for spinal cord ependymomas. Only manuscripts with clearly defined age, tumor grade, extent of resection, and clinical follow-up were included.ResultsA total of 80 patients were identified with a histologic distribution as follows: 36 % myxopapillary (grade I), 54 % classical (grade II), and 10 % anaplastic (grade III). There was no association between tumor grade and PFS. The only factor associated with improved PFS was gross total resection (GTR), which remained significant in a multivariate model (hazard ratio (HR) = 0.248, p = 0.022). Moreover, older age (HR = 0.818, p = 0.026), GTR (HR = 0.042, p = 0.013), and anaplastic grade (HR = 19.847, p = 0.008) demonstrated a significant association with OS in a multivariate model.ConclusionsAmong pediatric patients with spinal cord ependymomas, PFS did not differ across histologic grades but was prolonged among patients who underwent GTR. Age, extent of resection, and tumor grade were all significantly associated with survival.

Rationale and Objectives: To evaluate the results of 18F-FDG PET/MRI in relation to the histopathologic subtypes and histologic grades of mass-forming primary intrahepatic neoplasms.Materials and Methods: We retrospectively evaluated 18F-FDG positron emission tomography/magnetic resonance imaging (PET/MRI) results for 39 patients with histopathologically confirmed primary hepatic neoplasms, 15 with mass-forming intrahepatic cholangiocarcinoma (ICC) and 24 with hepatocellular carcinoma (HCC). The apparent diffusion coefficient (ADC) and standardized uptake value (SUV) were analyzed in relation to the histopathologic diagnosis and histologic grade, including calculating the sensitivity and specificity of the imaging findings.Results: The median SUV of ICC (6.0 [interquartile range, 5-10]) was significantly higher than that of HCC (4.0 [2.62-6.50]) (p = 0.002). An area under the curve (AUC) of 0.79 (95% confidence interval 0.649-0.932) had a sensitivity of 86.7% and a specificity of 67% at the best cut-off SUV of 4.41 to differentiate between ICC and HCC. ADC values did not differ significantly between HCCs and ICCs (p = 0.283). Both SUV and ADC values differed significantly between low-grade (well- and moderately differentiated) and high-grade (poorly differentiated) HCCs. Combining ADC and SUV further improved differentiation of low- from high-grade HCCs to a significant level (0.929). The SUV did not differ significantly between ICC histologic grades (p = 0.280), while the ADC differed significantly only between well and poorly differentiated ICCs (p = 0.004).Conclusion: Assessing primary hepatic neoplasms with 18F-Fluorodeoxyglucose PET/MRI may help to predict tumor grade and differentiate between types of intrahepatic neoplasms. [ABSTRACT FROM AUTHOR]

Background: Preoperative grading of hepatocellular carcinoma (HCC) is an important factor associated with prognosis after liver resection. The promising prediction of the differentiation of HCC remains a challenge. The purpose of our study was to investigate the value of amide proton transfer (APT) imaging in predicting the histological grade of HCC, compared with the intravoxel incoherent motion (IVIM) imaging.Methods: From September 2018 to February 2020, 88 patients with HCC were enrolled and divided into four groups (G1, G2, G3, and G4) based on the histologic grades. Preoperative APT signal intensity (SI), apparent diffusion coefficient (ADC), true molecular diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f ) of HCC were independently measured by two radiologists. The averaged values of those parameters were compared using an analysis of variance. The Spearman rank analysis was used to compare the correlation between those imaging parameters and the histological grades. Receiver operating characteristic (ROC) curve analysis was used to explore the predictive performance.Results: There were significant differences in APT SI, ADC, D, and f among the four grades of HCC (all P < 0.001). A moderate to good relationship was found between APT SI and the histologic grade of HCC (r = 0.679, P < 0.001). APT SI had an area under the ROC curve (AUC) of 0.890 (95% CI: 0.805–0.947) for differentiating low- from high-grade HCC, and the corresponding sensitivity and specificity were 85.71% and 82.05%, respectively. Comparison of ROC curves demonstrated that the AUC of APT SI was significantly higher than those of IVIM-derived parameter (Z = 2.603, P = 0.0092; Z = 2.099, P = 0.0358; Z = 4.023, P = 0.0001; Z = 2.435, P = 0.0149, compared with ADC, D, D*, and f , respectively). Moreover, the combination of both techniques further improved the diagnostic performance, with an AUC of 0.929 (95% CI: 0.854–0.973).Conclusion: APT imaging may be a potential noninvasive biomarker for the prediction of histologic grading of HCC and complements IVIM imaging for the more accurate and comprehensive characterization of HCC.

Abstract Hepatocellular carcinoma (HCC) is one of the most common human solid malignancies worldwide. Although the MRI is the technique that is best adapted to characterize HCC, there is not an agreement regarding the study protocol and even what the role of Diffusion-weighted imaging (DWI). The possibility that imaging study can correlate to histologic grade to selecting the therapeutic strategy would be valuable in helping to direct the proper management of HCC. Apparent Diffusion Coefficient (ADC) and IVIM-derived perfusion fraction (fp) and tissue diffusivity (Dt) values of HCC showed significantly better diagnostic performance in differentiating high-grade HCC from low-grade HCC, and significant correlation was observed between ADC, fp, Dt and histological grade.

Background: Preoperative grading of hepatocellular carcinoma (HCC) is an important factor associated with prognosis after liver resection. The promising prediction of the differentiation of HCC remains a challenge. The purpose of our study was to investigate the value of amide proton transfer (APT) imaging in predicting the histological grade of HCC, compared with the intravoxel incoherent motion (IVIM) imaging. Methods: From September 2018 to February 2020, 88 patients with HCC were enrolled and divided into four groups (G1, G2, G3, and G4) based on the histologic grades. Preoperative APT signal intensity (SI), apparent diffusion coefficient (ADC), true molecular diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) of HCC were independently measured by two radiologists. The averaged values of those parameters were compared using an analysis of variance. The Spearman rank analysis was used to compare the correlation between those imaging parameters and the histological grades. Receiver operating characteristic (ROC) curve analysis was used to explore the predictive performance. Results: There were significant differences in APT SI, ADC, D, and f among the four grades of HCC (all P < 0.001). A moderate to good relationship was found between APT SI and the histologic grade of HCC (r = 0.679, P < 0.001). APT SI had an area under the ROC curve (AUC) of 0.890 (95% CI: 0.805–0.947) for differentiating low- from high-grade HCC, and the corresponding sensitivity and specificity were 85.71% and 82.05%, respectively. Comparison of ROC curves demonstrated that the AUC of APT SI was significantly higher than those of IVIM-derived parameter (Z = 2.603, P = 0.0092; Z = 2.099, P = 0.0358; Z = 4.023, P = 0.0001; Z = 2.435, P = 0.0149, compared with ADC, D, D*, and f , respectively). Moreover, the combination of both techniques further improved the diagnostic performance, with an AUC of 0.929 (95% CI: 0.854–0.973). Conclusion: APT imaging may be a potential noninvasive biomarker for the prediction of histologic grading of HCC and complements IVIM imaging for the more accurate and comprehensive characterization of HCC. [ABSTRACT FROM AUTHOR]

Background: In the molecular era, the relevance of tumor grade for prognostication of IDH1/2‐wildtype (WT) gliomas has been debated. It has been suggested that histologic grade II and III astrocytomas with molecular features of glioblastoma, IDH1/2‐WT have a similar prognosis to glioblastoma and should be considered for the same clinical trials. Methods: We integrated prospective clinical sequencing from 564 patients with IDH1/2‐WT gliomas (26 grade II, 71 grade III and 467 grade IV) with clinical and radiographic data to assess associations between molecular features, grade and outcome. Results: Compared to histologic grade IV IDH1/2‐WT astrocytomas, histologic grade II astrocytomas harbor fewer chromosome 7/10 alterations (P = 0.04), EGFR amplifications (P = 0.022) and alterations in cell‐cycle effectors (P = 1.9e‐11), but a similar frequency of TERT promoter mutations. In contrast, there is no difference in the frequency of these canonical molecular features in histologic grade III vs. IV IDH1/2‐WT disease. Progression‐free (PFS) and overall survival (OS) for histologic grade II tumors were significantly longer than grade III tumors (P = 0.02 and P = 0.008, respectively), whereas there was no difference in PFS and OS for histologic grade III compared to grade IV tumors. Median PFS for histologic grade II, III and IV tumors was 19, 11 and 9 months, respectively. Median OS for the same tumors was 44, 23 and 23 months, respectively. In histologic grade II and III IDH1/2 WT tumors, gliomatosis is associated with the absence of cell‐cycle alterations (P = 0.008) and enriched in grade II features (P = 0.1) and alterations in the PI3K‐AKT pathway (P = 0.09). Conclusions: Grade II histology has genotypic and phenotypic associations with prognostic implications in IDH1/2‐WT astrocytomas. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is one of the most common cancers with high mortality globally. However, the molecular mechanisms of GC are unclear, and the prognosis of GC is poor. Therefore, it is important to explore the underlying mechanisms and screen for novel prognostic markers and treatment targets. Methods: The genetic and clinical data of GC patients in The Cancer Genome Atlas (TCGA) was analyzed by weighted gene co-expression network analysis (WGCNA). Modules with clinical significance and preservation were distinguished, and gene ontology and pathway enrichment analysis were performed. Hub genes of these modules were validated in the TCGA dataset and another independent dataset from the Gene Expression Omnibus (GEO) database by t-test. Furthermore, the significance of these genes was confirmed via survival analysis. Results: We found a preserved module consisting of 506 genes was associated with clinical traits including pathologic T stage and histologic grade. PDGFRB, COL8A1, EFEMP2, FBN1, EMILIN1, FSTL1 and KIRREL were identified as candidate genes in the module. Their expression levels were correlated with pathologic T stage and histologic grade, also affected overall survival of GC patients. Conclusion: These candidate genes may be involved in proliferation and differentiation of GC cells. They may serve as novel prognostic markers and treatment targets. Moreover, most of them were first reported in GC and deserved further research. [ABSTRACT FROM AUTHOR]

Due in part to remarkable advances over the past decade in our understanding of lung cancer, particularly in area of medical oncology, molecular biology, and radiology, there is a pressing need for a revised classification, based not on pathology alone, but rather on an integrated multidisciplinary approach to classification of lung cancer. The 2015 World Health Organization (WHO) Classification of Tumors of the Lung, Pleura, Thymus and Heart has just been published with numerous important changes from the 2004 WHO classification. The revised classification has been greatly improved in helping advance the field, increasing the impact of research, improving patient care and assisting in predicting outcome. The most significant changes will be summarized in this paper as follows: (1) main changes of lung adenocarcinoma as proposed by the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification, (2) reclassifying squamous cell carcinomas into keratinizing, nonkeratinizing, and basaloid subtypes with the nonkeratinizing tumors requiring immunohistochemistry proof of squamous differentiation, (3) restricting the diagnosis of large cell carcinoma only to resected tumors that lack any clear morphologic or immunohistochemical differentiation with reclassification of the remaining former large cell carcinoma subtypes into different categories, (4) grouping of neuroendocrine tumors together in one category, (5) and the current viewpoint of histologic grading of lung cancer.

Background and objectives: Our aim is to explore the relationship between the levels of protein encoded by Ki67 and the histopathological aspects regarding the overall survival and progression-free survival in a single university center. A secondary objective was to examine other factors that can influence these endpoints. New approaches to the prognostic assessment of breast cancer have come from molecular profiling studies. Ki67 is a nuclear protein associated with cell proliferation. Together with the histological type and tumor grade, it is used to appreciate the aggressiveness of the breast tumors. Materials and Methods: We conducted a retrospective single-institution study, at Elias University Emergency Hospital, Bucharest, Romania, in which we enrolled women with stage I to III breast cancer. The protocol was amended to include the immunohistochemistry determination of Ki67 and the histological aspects. The methodology consisted in using a Kaplan–Meier analysis for the entire sample and restricted mean survival time up to 36 months. Results: Both lower Ki67 and low tumor grade are associated with better prognosis in terms of overall survival (OS) and progression-free survival (PFS) for our patients’ cohort. In our group, the histological type did not impact the time to progression or survival. Conclusions: Both overall survival and progression-free survival may be influenced by the higher value of Ki67 and less differentiated tumors. Further studies are needed in order to establish if the histologic type may impact breast cancer prognostic, probably together with other histologic and molecular markers.

Background Gastric cancer (GC) is one of the most common cancers with high mortality globally. However, the molecular mechanisms of GC are unclear, and the prognosis of GC is poor. Therefore, it is important to explore the underlying mechanisms and screen for novel prognostic markers and treatment targets. Methods The genetic and clinical data of GC patients in The Cancer Genome Atlas (TCGA) was analyzed by weighted gene co-expression network analysis (WGCNA). Modules with clinical significance and preservation were distinguished, and gene ontology and pathway enrichment analysis were performed. Hub genes of these modules were validated in the TCGA dataset and another independent dataset from the Gene Expression Omnibus (GEO) database by t-test. Furthermore, the significance of these genes was confirmed via survival analysis. Results We found a preserved module consisting of 506 genes was associated with clinical traits including pathologic T stage and histologic grade. PDGFRB, COL8A1, EFEMP2, FBN1, EMILIN1, FSTL1 and KIRREL were identified as candidate genes in the module. Their expression levels were correlated with pathologic T stage and histologic grade, also affected overall survival of GC patients. Conclusion These candidate genes may be involved in proliferation and differentiation of GC cells. They may serve as novel prognostic markers and treatment targets. Moreover, most of them were first reported in GC and deserved further research.

Accurate staging of esophageal cancer is very important to achieving optimal treatment outcomes. The AJCC (American Joint Committee on Cancer) first published TNM esophageal cancer staging recommendations in the first edition of their staging manual in 1977. Thereafter, the staging of esophageal cancer was changed many times over the years. This article reviews the current status of staging of esophageal cancer.

Rationale and Objectives To develop and validate a computed tomography-based radiomics signature for preoperatively discriminating high-grade from low-grade colorectal adenocarcinoma (CRAC). Materials and Methods This retrospective study was approved by our institutional review board, and the informed consent requirement was waived. This study enrolled 366 patients with CRAC (training dataset: n = 222, validation dataset: n = 144) from January 2008 to August 2015. A radiomics signature was developed with the least absolute shrinkage and selection operator method in training dataset. Mann-Whitney U test was applied to explore the correlation between radiomics signature and histologic grade. The discriminative power of radiomics signature was investigated with the receiver operating characteristics curve. An independent validation dataset was used to confirm the predictive performance. We further performed a stratified analysis to validate the predictive performance of radiomics signature in colon adenocarcinoma and rectal adenocarcinoma. Results The radiomics signature demonstrated discriminative performance for high-grade and low-grade CRAC, with an area under the curve of 0.812 (95% confidence interval [CI]: 0.749–0.874) in training dataset and 0.735 (95%CI: 0.644–0.826) in validation dataset. Stratified analysis demonstrated that radiomics signature also showed distinguishing ability for histologic grade in both colon adenocarcinoma and rectal adenocarcinoma, with area under the curve of 0.725 (95%CI: 0.653–0.797) and 0.895 (95%CI: 0.838–0.952), respectively. Conclusions We developed and validated a radiomics signature as a complementary tool to differentiate high-grade from low-grade CRAC preoperatively, which may make contribution to personalized treatment. [ABSTRACT FROM AUTHOR]

Activating epidermal growth factor receptor (EGFR) mutations in metastatic non-small cell lung cancer (NSCLC) are associated with a high response rate to EGFR tyrosine kinase inhibitor (TKI). The current guidelines recommend routine EGFR mutational analysis prior to initiating first line systemic therapy. The clinical characteristics including smoking status, histologic type, sex and ethnicity are known to be associated with the incidence of EGFR mutations. We retrospectively analyzed 277 patients with metastatic NSCLC within Kaiser Permanente Northern California (KPNC); among these patients, 83 were positive for EGFR mutations. We performed both univariate and multivariable logistic regressions to identify predictors of EGFR mutations. We found that histologic grade was significantly associated with the incidence of EGFR mutation, regardless of ethnicity, sex and smoking status. In grade I (well differentiated) and II (moderately differentiated), histology was associated with significantly higher incidence of EGFR mutations compared to grade II-III (moderate-to-poorly differentiated) and III (poorly differentiated). Ever-smokers with grade III lung adenocarcinoma had 1.8% incidence of EGFR mutations. This study indicates that histologic grade is a predictive factor for the incidence of EGFR mutations and suggests that for patients with grade II-III or III lung adenocarcinoma, prompt initiation of first-line chemotherapy or immunotherapy is appropriate while awaiting results of EGFR mutational analysis, particularly for patients with history of smoking. [ABSTRACT FROM AUTHOR]