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Objectives Novel histopathologic prognostic factors are needed to identify patients with follicular lymphoma (FL) at risk of inferior outcomes. Our primary objective was to evaluate the Ki-67 proliferative index in follicular and interfollicular areas in tissue biopsy specimens from patients with newly diagnosed FL and correlate with clinical outcomes. Our secondary objective was to correlate PD-L1 and LAG-3 with clinical outcomes. Methods Seventy cases of low-grade FL from the University of Minnesota were evaluated with Ki-67 immunohistochemical stain. Ki-67 expression as a continuous variable was interpreted digitally and manually in follicular and interfollicular areas. Progression-free survival (PFS) and overall survival (OS) were analyzed by Cox regression, and hazard ratios (HRs) per 10-point increase in Ki-67 were calculated. Results Progression-free survival at 4 years was 28% (95% CI, 19%-41%). Interfollicular, but not follicular, Ki-67 was associated with PFS by manual (HR, 1.33; P =.01) and digital (HR, 1.38; P =.02) analysis. Digital and manual Ki-67 were only moderately correlated but demonstrated similar effects on PFS. At 4 years, OS was 90% with no association with follicular or interfollicular Ki-67 proliferation. Conclusions Higher interfollicular Ki-67 by either digital or manual analysis is associated with a poorer PFS in patients with low-grade FL. These results suggest further validation of this marker is warranted to improve pathologic risk stratification at FL diagnosis. PD-L1 and LAG-3 were not associated with PFS or OS. [ABSTRACT FROM AUTHOR]

Background: Despite initial response to platinum-based chemotherapy and PARP inhibitor therapy (PARPi), nearly all recurrent high-grade serous ovarian cancer (HGSC) will acquire lethal drug resistance; indeed, ~15% of individuals have de novo platinum-refractory disease. Objectives: To determine the potential of anti-microtubule agent (AMA) therapy (paclitaxel, vinorelbine and eribulin) in platinum-resistant or refractory (PRR) HGSC by assessing response in patient-derived xenograft (PDX) models of HGSC. Design and methods: Of 13 PRR HGSC PDX, six were primary PRR, derived from chemotherapy-naïve samples (one was BRCA2 mutant) and seven were from samples obtained following chemotherapy treatment in the clinic (five were mutant for either BRCA1 or BRCA2 (BRCA1/2), four with prior PARPi exposure), recapitulating the population of individuals with aggressive treatment-resistant HGSC in the clinic. Molecular analyses and in vivo treatment studies were undertaken. Results: Seven out of thirteen PRR PDX (54%) were sensitive to treatment with the AMA, eribulin (time to progressive disease (PD) ⩾100 days from the start of treatment) and 11 out of 13 PDX (85%) derived significant benefit from eribulin [time to harvest (TTH) for each PDX with p < 0.002]. In 5 out of 10 platinum-refractory HGSC PDX (50%) and one out of three platinum-resistant PDX (33%), eribulin was more efficacious than was cisplatin, with longer time to PD and significantly extended TTH (each PDX p < 0.02). Furthermore, four of these models were extremely sensitive to all three AMA tested, maintaining response until the end of the experiment (120d post-treatment start). Despite harbouring secondary BRCA2 mutations, two BRCA2 -mutant PDX models derived from heavily pre-treated individuals were sensitive to AMA. PRR HGSC PDX models showing greater sensitivity to AMA had high proliferative indices and oncogene expression. Two PDX models, both with prior chemotherapy and/or PARPi exposure, were refractory to all AMA, one of which harboured the SLC25A40-ABCB1 fusion, known to upregulate drug efflux via MDR1. Conclusion: The efficacy observed for eribulin in PRR HGSC PDX was similar to that observed for paclitaxel, which transformed ovarian cancer clinical practice. Eribulin is therefore worthy of further consideration in clinical trials, particularly in ovarian carcinoma with early failure of carboplatin/paclitaxel chemotherapy. [ABSTRACT FROM AUTHOR]

Papillary glioneuronal tumors are rare neoplasm, accounting only <0.02% of all intracranial tumors. They are generally low grade usually occur in the temporal lobe near the third ventricle. We report an extremely rare case of intraventricular tumor with a high proliferation index. CD 117 expression found in our case is the first study to the best of our knowledge to be described in these tumors. The clinical and diagnostic significance of this finding is subject to further studies. [ABSTRACT FROM AUTHOR]

Introduction: Astrocytomas are the commonest primary Central Nervous System (CNS) tumours. Its diagnosis is based on histopathological criteria defined by the World Health Organization (WHO) 2016 that grades astrocytoma into four grades. The subjective nature of WHO grading has prompted for more objective methods to evaluate nuclear features. Furthermore, Ki-67, a marker of cellular proliferation is a useful diagnostic tool that also helps in prognostic evaluation and to plan adjuvant therapy in astrocytomas. Aim: To evaluate the nuclear morphometry and Ki-67 proliferative marker in astrocytomas and to assess the relationship of WHO grade with proliferative activity using Ki-67 immunostaining. Materials and Methods: This ambispective study was conducted in the Department of Pathology, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India, with a total duration of four years (October 2017 to September 2021). From 35 astrocytoma cases, Haematoxylin and Eosin (H&E) stained slides were retrieved and reviewed appropriately by two pathologists and graded using the WHO criteria. Nuclear morphometric analysis was performed on the H&E slides using Olympus BX-41 research microscope. The parameters evaluated were mean nuclear length, mean nuclear diameter, mean nuclear perimeter, mean nuclear area, Mean Nuclear Roundness Factor (MNRF) and mean nuclear ellipse form. The cases were then stained with Ki-67 antibody. The relationships between WHO grade of astrocytoma and nuclear morphometry and WHO grade with proliferative index was analysed. Results: According to WHO grading, four cases were Grade 1 (11.4%), 12 grade 2 (34.3%), six grade 3 (17.1%) and 13 grade 4 (37.1%). Significant correlation was seen between WHO grading and mean nuclear length, diameter, perimeter, area and Ki-67 with p-value of less than 0.001. Conclusion: Astrocytoma is an extremely heterogeneous disease with unpredictable outcome. The widely used WHO grading is subjective, while nuclear morphometry, using computer assisted image analysis, can ensure more objective assessment. The Ki-67 index could provide valuable information and may compliment the other parameters. [ABSTRACT FROM AUTHOR]

Introduction: Astrocytomas are the commonest primary Central Nervous System (CNS) tumours. Its diagnosis is based on histopathological criteria defined by the World Health Organisation (WHO) 2016 that grades astrocytoma into four grades. The subjective nature of WHO grading has prompted for more objective methods to evaluate nuclear features. Furthermore, Ki-67, a marker of cellular proliferation is a useful diagnostic tool that also helps in prognostic evaluation and to plan adjuvant therapy in astrocytomas. Aim: To evaluate the nuclear morphometry and Ki-67 proliferative marker in astrocytomas and to assess the relationship of WHO grade with proliferative activity using Ki-67 immunostaining. Materials and Methods: This ambispective study was conducted in the Department of Pathology, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India, with a total duration of four years (October 2017 to September 2021). From 35 astrocytoma cases, Haematoxylin and Eosin (H&E) stained slides were retrieved and reviewed appropriately by two pathologists and graded using the WHO criteria. Nuclear morphometric analysis was performed on the H&E slides using Olympus BX-41 research microscope. The parameters evaluated were mean nuclear length, mean nuclear diameter, mean nuclear perimeter, mean nuclear area, Mean Nuclear Roundness Factor (MNRF) and mean nuclear ellipse form. The cases were then stained with Ki-67 antibody. The relationships between WHO grade of astrocytoma and nuclear morphometry and WHO grade with proliferative index was analysed. Results: According to WHO grading, 4 (11.4%) cases were grade 1, 12 (34.3%) grade 2, six (17.1%) grade 3 and 13 (37.1%) grade 4. Significant correlation was seen between WHO grading and mean nuclear length, diameter, perimeter, area and Ki-67 with p-value

Introduction: The proper management of the astrocytic tumours largely depends on its correct diagnosis. But, smaller size and complicated histomorphology makes it difficult for the histopathologist to conclude the diagnosis. Monoclonal antibody Ki-67 {MIB-1/MIB-1 Labelling Index (LI)} plays a role of diagnostic as well as prognostic marker. It is an important marker, since it helps in deciding malignant potential of the astrocytic tumours where histology alone does not suffice. This study promotes the idea of including Ki-67 in routine practice for astrocytic tumours as it helps in quantifying the growth of the tumour which is of utmost importance in predicting the outcome accurately. Aim: The aim of this study was to determine the mean and ranges of Ki-67/MIB-1 LI in astrocytic tumours and comparing between different grades. Materials and Methods: This was a hospital based crosssectional study with 50 cases of astrocytoma of varying grades over period of six years, retrospective study period started from 1st April 2009 till 30th November 2012 and prospective study period started from 1st December 2012 till 31st March 2014. Immunolabeling was done using Ki-67/MIB-1 antibody. The mean and ranges of Ki-67 was calculated in astrocytic tumours and its correlation with each World Health Organization (WHO) grade of histological diagnosis and clinical presentations were studied. One-way Analysis of Variance (ANOVA) and unpaired t-test were used for statistical analysis. Results: There were 50 astrocytic tumours, Pilocytic Astrocytoma (PA), grade I-5 (10%) cases; Diffuse Astrocytoma (DA), grade II-8 (16%) cases; Anaplastic Astrocytoma (AA), grade III-10 (20%) cases; and Glioblastoma Multiforme (GBM), grade IV-27 (54%) cases, with mean Ki-67 LI as 2.63%, 2.65%, 18.85% and 30.2%, respectively. The difference in mean Ki-67 LI for low grade astrocytoma and high grade astrocytoma was highly significant statistically (p

Introduction/Objective. The aim of this study is to examine the association of E-cadherin expression and high proliferation index (proIDX) with clinical and pathological indicators of colorectal cancer progression. Methods. The biopsy of 72 patients, obtained by resection of colorectal cancer, was routinely processed at the Institute of Pathology of the Clinical Centre of Montenegro, embedded in paraffin and archived. Based on the archived pathohistological reports, two study groups were formed: the first group (n = 72) consisted of operative biopsies of colorectal cancer, and the control group (n = 72) consisted of biopsies of adjacent non-tumor tissue. Routine hematoxylin-eosin and immunohistochemical avidin-biotin-peroxidase complex method with anti-Ki67 and anti-E-cadherin antibodies was applied on. After quantification of the results for statistical tests, the software package SPSS for Windows (19.0) was used. Results. In colorectal carcinoma, we observed a significant association of proIDX with pT stage, lymph and blood vessel invasion, perineural invasion, lymph node metastases and distant metastases, and Astler–Coller stage tumor disease. We also observed that the absence of E-cadherin was significantly associated with pT stage, lymph and blood vessel invasion, perineural invasion with lymph node metastases, distant metastases, with C2 and D Astler–Coller tumor stage. E-cadherin expression is associated with proIDX with a significantly high, negative correlation coefficient. Conclusion. Our results indicate that it is possible to differentiate patients into groups with a higher or lower risk of developing metastatic disease, based on the expression of Ki67 and E-cadherin.

Introduction: Argyrophilic nucleolar organizer regions (AgNORs) are nonhistone argyrophilic nucleolar proteins associated with ribosomal genes found in the nucleolar organizer region that reflect cell proliferation and have an affinity for silver. AgNOR staining may be useful to evaluate prognosis in several neoplasms because higher AgNOR counts are related to higher grade tumors, metastases, and shorter survival times. Objective: We aimed to report on a quick and practical technique to identify AgNORs adapted for use in routine cytology. Materials and methods: The cytopathologic diagnosis of mast cell tumor (MCT) in samples collected by fine‐needle aspiration (FNA) was determined. Next, slides were impregnated with a solution containing silver nitrate; the main modification of our technique included incubation of these slides at a controlled temperature of 25 °C. Some slides were previously stained with Diff‐Quik and others were only fixed with methanol. The slides were analyzed under a microscope, and the number of blackened intranuclear points (AgNORs) was counted. Results: Slides prestained with Diff‐Quik were easily counted compared with slides only fixed in methanol. Technical issues encountered with the methanol‐fixed slides included insufficient cellularity, background precipitation, and an absence of silver impregnation. Conclusions: The technique reported in this study showed satisfactory results for AgNOR counting in cytologic smears from MCT, such as good impregnation and the elimination of background interferents. Further evaluation of this method comparing AgNOR counts with histologic examinations, tumor grades, other prognostic markers, and survival times are needed to fully evaluate the benefit of this technique. [ABSTRACT FROM AUTHOR]

This study aims to investigate the utility of digital protocols for Ki-67 immunohistochemistry quantitative analysis ("hot spot" method) in the setting of well-differentiated hepatocellular neoplasms. Resection cases of typical hepatic adenomas (HAs) (n = 40), atypical HAs (n = 9), and well-differentiated hepatocellular carcinomas (WD HCCs) (n = 56) were selected. HAs were further classified by immunohistochemistry using antibodies against liver fatty acid binding protein, glutamine synthetase, B-catenin, hepatic serum amyloid A, and C-reactive protein. Ki-67 proliferative index by immunohistochemistry was evaluated in all cases by digital analysis using a modified neuroendocrine tumor "hot spot" protocol. The proliferative rate of HAs (typical, median 1.2% (range 0–7.4%) and atypical, median 1.0% (range 0.3–3%)) was significantly lower than that of WD HCCs (median 4.5%, range 0–49.8%) (P < 0.0001). Only a few (7.5%) of the adenomas (all inflammatory/telangiectatic type) had proliferative rates higher than 4%, compared to most (51%) of HCCs. Ki-67 is a potentially useful adjunct marker in the evaluation of WD hepatocellular neoplasms, as "hot spot" proliferative rates are consistently very low in HAs but vary significantly in WD HCCs. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pediatric renal neoplasms comprise about 7%–8% of all neoplasms in children. Wilms tumour (WT) is the most common among pediatric renal tumours. AIMS AND OBJECTIVES: The study was undertaken to study the epidemiological occurrence of pediatric renal tumours in a tertiary care hospital and to ascertain the validity and reliability of touch smear imprint cytology in intraoperative diagnosis of renal tumours and correlate with subsequent histopathological diagnosis and to assess the expression of proliferation marker Ki-67 in different components and stages of WT. MATERIALS AND METHODS: It was a single-institution-based prospective and observational study, conducted for 2 years (from October 2013 to September 2015) in the department of pathology at our hospital. A total of fifty cases were enrolled in this study, all were below 15 years of age. RESULTS: Imprint cytology showed sensitivity, specificity, and diagnostic accuracy of 83%, 98%, and 95.74%, respectively, in diagnosing benign and malignant renal tumours. There was statistically significant correlation of imprint cytology with confirmatory histopathological examination of excision specimen (P < 0.001). Immunohistochemical analysis of Ki-67 was done in all WT cases. Epithelial component had higher proliferative index than blastemal component with P = 0.0082, which was highly statistically significant. CONCLUSION: Imprint cytology is found to be a less expensive, simple, and rapid method, which can be used as an adjunct to histopathology. Correlation between proliferation index as measured with Ki-67 antibody and tumour stage was found. Ki-67 is thus a relevant marker for assessing the proliferative activity.

Aims: Ki67 proliferative index (PI) is essential for grading gastroenteric and pancreatic neuroendocrine tumours (GEP NETs). Analytical and preanalytical variables can affect Ki67 PI. In contrast to counting methodology, until now little attention has focused on the question of clone equivalence and the effect of hot‐spot size on Ki67 PI in GEP NETs. Using manual counting and image analysis, this study compared the Ki67 PI achieved using MM1, K2 and 30‐9 to MIB1, a clone which has been validated for, and is referenced in, guidelines relating to assessment of Ki67 PI in GEP NETs. Methods and results: Forty‐two pancreatic NETs were each immunohistochemically stained for the anti‐Ki67 clones MIB1, MM1, K2 and 30‐9. Ki67 PI was calculated manually and by image analysis, the latter using three different hot‐spot sizes. In manual comparisons using single hot‐spot high‐power fields, non‐MIB1 clones overestimated Ki67 PI compared to MIB1, resulting in grading discordances. Image analysis shows good agreement with manual Ki67 PI but a tendency to overestimate absolute Ki67 PI. Increasing the size of tumour hot‐spot from 500 to 2000 cells resulted in a decrease in Ki67 PI. Conclusion: Different anti‐Ki67 clones do not produce equivalent PIs in GEP NETs, and clone selection may therefore affect patient care. Increasing the hot‐spot size decreases the Ki67 PI. Greater standardisation in terms of antibody clone selection and hot‐spot size is required for grading GEP NETs. Image analysis is an effective tool for assisting Ki67 assessment and allows easier standardisation of the size of the tumour hot‐spot. [ABSTRACT FROM AUTHOR]

Splenic hemangiosarcoma (HSA) is a malignant tumor of endothelial cells that affects middle-aged and elderly dogs and is characterized by the formation of new blood vessels, commonly associated with necrotic and hemorrhagic areas. Despite its importance in veterinary medicine, few studies have identified markers with prognostic value for canine HSA. Thus, this study aimed to associate the clinicopathological findings (prostate-specific membrane antigen [PSMA], Claudin-5, and Ki67 gene and protein expression) with overall survival in HSA-affected patients. Fifty-three formalin-fixed and paraffin-embedded canine splenic HSA samples, previously diagnosed by histopathological examination, were used in this study. Claudin-5, PSMA, and Ki67 protein expression levels were evaluated by immunohistochemistry, and gene expression was evaluated by quantitative polymerase chain reaction. Claudin-5 protein overexpression was observed in patients with metastasis (p = 0.0078) and with stage III tumors compared to those with stage I and II tumors (p = 0.0451). In patients treated with surgery alone, low PSMA gene and protein expression (p = 0.05 and p = 0.0355, respectively) were associated with longer survival time. Longer survival time was observed in patients with a low Ki67 index (p = 0.0488). Our results indicate that Claudin-5 protein expression is associated with metastatic status, and PSMA gene and protein expression, and Ki67 index are associated with survival time.

BACKGROUND: Meningiomas are the most common primary central nervous system neoplasms originating from the arachnoid cap cells and constitute between 13% and 26% of all intracranial tumors. AIMS AND OBJECTIVES: The aim of the study was to analyze the age-, sex-, and site-wise distribution of different histological patterns of meningiomas seen in our center and to assess the status of estrogen receptor (ER), progesterone receptor (PR), and proliferation marker Ki-67 in various grades of meningioma. MATERIALS AND METHODS: A prospective study was done in 90 cases. Patients presented with symptoms of headache and seizure and underwent subsequent excision surgery at Neurosurgery Department were taken. We have studied histological typing and grading of the tumors, and immunohistochemical staining was done for ER, PR, and Ki-67. STATISTICAL ANALYSIS: Two-group comparison was done using Mann–Whitney U-test and Fisher’s exact test. Comparison of Ki-67 expression between Grade 1 and Grade 2 meningiomas was determined using Mann–Whitney U-test. Comparison of ER and PR status between different histological grades was done by Fisher’s exact test. Two-tailed P < 0.001 was considered statistically significant. RESULTS: According to histological type, meningothelial meningioma is most common (38.8%) followed by transitional (22.2%). PR positivity is seen in 96.34% of Grade 1 tumors, and all Grade 2 tumors were PR negative (Fisher’s exact test P < 0.001). About 3.66% of Grade 1 and all Grade 2 tumors were positive for ER (Fisher’s exact test two-tailed P < 0.001). Mean Ki-67 labeling index (LI) was 2.57 ± 1.674 among Grade I tumors, 7.11 ± 1.084 in Grade II meningiomas. CONCLUSIONS: Most of Grade 1 meningiomas show PRs positivity and lack of ERs positivity. Meningiomas with higher proliferation index and negative PR are very likely to be Grade II or Grade III. Evaluation of ER, PR status, and Ki-67 labeling index (LI) with histological evaluation helps us in providing information about the biologic behavior of meningiomas.

Introduction: In the majority of malignant tumours including salivary glands tumours, the clinical stage and histological features are considered the most valuable prognostic and predictive factors for targeted therapy. Nevertheless, new prognostic factors for the Mucoepidermoid Carcinoma (MEC) are required due to the high rate of recurrence that occurs even with the early stage of the disease. The Adenoid Cystic Carcinoma (ACC) also needs more effective treatment as it show high rate of local recurrence and distant metastasis, even after surgical excision and radiotherapy. Aim: To assess the immunohistochemical expression of Tumour Associated Macrophage (TAMs) related marker (CD68) and proliferative marker (Ki-67) in salivary carcinomas (MEC and ACC). Furthermore, to study their correlation with clinicopathological factors, ERα, and HER-2 to detect the usefulness of these markers in the prognosis of such tumours. Materials and Methods: The present study was a crosssectional study conducted at Departments of Pathology, Surgery, Zagazig and Banha Universities, Egypt. The study included 37 salivary carcinomas (25 cases of MEC and 12 cases of ACC). The control group consisted of 10 normal salivary tissues. All paraffin blocks were dissected and stained with H&E to confirm the diagnosis and grade the tumours. IHC expression of CD68 and Ki-67 was assessed in all the cases and further correlated with clinicopathological factors, ERα and HER-2. Results: High TAMs was detected in 64.0% of MEC and 41.7% of ACC. High TAMs was significantly detected in high grades (p=0.006 and 0.045 for MEC and ACC respectively), in advanced stage (p=0.033 and 0.015 for MEC and ACC respectively), and in larger MEC (p=0.017). Ki-67 was significantly expressed in MEC compared to ACC (p=0.046), it was significantly expressed in high-grades MEC (p=0.011) and ACC (p=0.01). ERα was detected in 16.0% of MEC and 25.0% of ACC. HER-2 was detected in 12.0% of MEC and 16.7% of ACC. Correlation between CD68 and Ki-67 among the studied carcinomas revealed a significant moderate positive correlation (r=0.449, p=0.005). Conclusion: High level of TAMs expressed by CD68 and high proliferative activity measured by Ki-67 could be regarded as a poor prognostic parameter in MEC and ACC. A strong correlation between both markers was found, thus controlling the level of TAMs may have promoting role in targeted therapy. However, these results pointed towards a limited application of ERα and HER-2 in targeted therapy due to limited expressions in the present studied carcinomas.

Introduction: In the majority of malignant tumours including salivary glands tumours, the clinical stage and histological features are considered the most valuable prognostic and predictive factors for targeted therapy. Nevertheless, new prognostic factors for the Mucoepidermoid Carcinoma (MEC) are required due to the high rate of recurrence that occurs even with the early stage of the disease. The Adenoid Cystic Carcinoma (ACC) also needs more effective treatment as it show high rate of local recurrence and distant metastasis, even after surgical excision and radiotherapy. Aim: To assess the immunohistochemical expression of Tumour Associated Macrophage (TAMs) related marker (CD68) and proliferative marker (Ki-67) in salivary carcinomas (MEC and ACC). Furthermore, to study their correlation with clinicopathological factors, ERα, and HER-2 to detect the usefulness of these markers in the prognosis of such tumours. Materials and Methods: The present study was a cross-sectional study conducted at Departments of Pathology, Surgery, Zagazig and Banha Universities, Egypt. The study included 37 salivary carcinomas (25 cases of MEC and 12 cases of ACC). The control group consisted of 10 normal salivary tissues. All paraffin blocks were dissected and stained with H&E to confirm the diagnosis and grade the tumours. IHC expression of CD68 and Ki-67 was assessed in all the cases and further correlated with clinicopathological factors, ERα and HER-2. Results: High TAMs was detected in 64.0% of MEC and 41.7% of ACC. High TAMs was significantly detected in high grades (p=0.006 and 0.045 for MEC and ACC respectively), in advanced stage (p=0.033 and 0.015 for MEC and ACC respectively), and in larger MEC (p=0.017). Ki-67 was significantly expressed in MEC compared to ACC (p=0.046), it was significantly expressed in high-grades MEC (p=0.011) and ACC (p=0.01). ERα was detected in 16.0% of MEC and 25.0% of ACC. HER-2 was detected in 12.0% of MEC and 16.7% of ACC. Correlation between CD68 and Ki-67 among the studied carcinomas revealed a significant moderate positive correlation (r=0.449, p=0.005). Conclusion: High level of TAMs expressed by CD68 and high proliferative activity measured by Ki-67 could be regarded as a poor prognostic parameter in MEC and ACC. A strong correlation between both markers was found, thus controlling the level of TAMs may have promoting role in targeted therapy. However, these results pointed towards a limited application of ERα and HER-2 in targeted therapy due to limited expressions in the present studied carcinomas. [ABSTRACT FROM AUTHOR]

Abstract The most important microscopic characteristic of Cyclosporine A-induced gingival overgrowth is fibroepithelial hyperplasia. Objective: The objective was to investigate the influence of previous exposure to Cyclosporine A over gingival epithelium in experimental periodontitis in rats. Methods: Twenty Wistar rats with 12 weeks-old were divided into four groups with 5 animals each: Control Group (CG); Cyclosporine Group (CsAG); Ligature group (LG) and Cyclosporine and Ligature Group (CsALG). Daily doses of CsA (10 mg/kg) were applied to CsAG and CsALG during 60 days since the beginning of the experiment and, a ligature was placed in LG and CsALG 30 days after the beginning of the experiment. After 60 days, animals were euthanized and gingival tissue was processed to histomorphometric analysis of epithelial thickness (mm2), immunohistochemical expression of PCNA (%) and inflammatory response. Data were analyzed by Kruskal-Wallis and Mann Whitney at 0.05 significance level. Results: Considering epithelial thickness, CG was thinner than all groups, CsALG was the largest and CsAG and LG were similar between each other. Regarding the PCNA expression CG (16.46 ± 9.26) was similar to CsAG (34.47 ± 19.75) and, LG (59.02 ± 10.33) was similar to CsALG (40.59 ± 18.25). Significant difference (p < 0.05) occurred only in inflammation presence comparing CG/LG and CsAG/CsALG. A weak positive correlation between the number of PCNA+ and inflammatory cells (p = 0.001; r = 0.611) was observed. Conclusion: Based on these results it was concluded that the enlargement of gingival epithelium observed in experimental periodontitis can be increased by previous exposition to CsA and inflammatory conditions enhanced proliferative activity of the keratinocytes. [ABSTRACT FROM AUTHOR]

Abstract Objective New proliferative marker MCM-2 can be observed in all phases of cell cycle and plays a central role in chromatin replication. At present limited information exists on the expression of MCM-2 in odontogenic pathologies (OP). Hence, the purpose was to assess the expression of Ki-67 and MCM-2 in clinically significant OP and to evaluate the relation between these markers and the clinical-imaging-pathologic characteristics of ameloblastoma (AM) and odontogenic keratocyst (OKC). Materials and Methods: Clinical-imaging-pathologic characteristics of thirty consecutive cases of AM and thirty OKC were tabulated and sections were subjected to immunostaining for Ki-67 and MCM-2. The quantitative data was subjected to One Way Anova, Tukeys multiple posthoc procedures, independent t -test, paired t -test and Pearson's correlation test. Results Proliferative index (PI) was significantly higher with MCM-2 than Ki-67 in AM and OKC. PI with Ki-67 and MCM-2 in AM was significantly higher in peripheral than the central cells. PI with Ki-67 and MCM-2 in OKC was significantly higher in suprabasal than the basal cells. PI with Ki-67 or MCM-2 in AM and OKC did not show a statistically significant difference. MCM-2 in AM showed a significant association with type of radiolucency and nature of lesion. Ki-67 in OKC showed a significant association with number of lesion and type of radiolucency. Conclusions MCM-2 is a more sensitive marker for assessing the growth rate, and may be appropriate in sorting the proliferative fraction than Ki-67. Comparable expression of proliferative markers in AM and OKC clarifies their nature, indicating identical aggressive character. [ABSTRACT FROM AUTHOR]

P53 is important for cell cycle regulation, and its overexpression is seen in malignant tumors. We examined correlation between p53 expression and cell proliferation, and its role in the pathogenesis of keratinocyte skin tumors. We used biopsies from patients with squamous cell carcinoma, actinic keratosis and keratoacanthoma. We examined crosssections stained with HE and using anti-cytokeratin, antip53 and anti-Ki67 antibodies. Expression of p53 is found in 87, 85% of SCC, in 83. 3% of AK and 13. 4% KA. The high index of p53 expression was higher in SCC and AK compared to KA. We also observed a positive correlation between the expression of p53 and localization of the tumors. The largest proportion of subjects with AK and SCC has a high index of p53 expression on photoexposed region. We also observed that p53 expression correlates with age whereby in AK p53 expression increases with age. The high index of proliferation is most frequent in SCC and KA. Also at AK we found a strong correlation between a moderate proliferation index and tumor localization in photoexposed region. Between the proliferation index and p53 expression we observed a significant positive correlation only in SCC. Proliferation index and the expression of p53 are useful for the differentiation of precursor keratinocyte lesions and skin carcinoma. High p53 expression has been associated with the aging and significantly correlates with the exposure to UV radiation in SCC and AK. High expression of p53 in AK and SCC supports the importance of this oncoprotein in carcinogenesis of the skin. [ABSTRACT FROM AUTHOR]

Background/Aims: Pilocytic astrocytomas are common pediatric tumors. Molecular profiles vary with location of origin. Comparisons of proliferation have not been reported. We sought to identify differences in growth by region and whether these predict clinical behavior. Methods: A retrospective review of all patients undergoing surgery for a pilocytic astrocytoma at Children's Hospital LA from 2003 to 2015 was completed. Tumor location, determined by imaging, was stratified into infratentorial, supratentorial, or optic pathway. Proliferation was measured by Ki-67 immunostaining. A p value of 0.05 was deemed significant. Results: 77 patients were identified. 51 had posterior fossa tumors, 12 had supratentorial tumors, and 14 had optic pathway tumors. Mean Ki-67 score was 3.67, 4.09, and 3.83%, respectively (p = 0.82). Ki-67 of ≥4% trended towards recurrence (p = 0.11), incomplete resection (p = 0.15), and younger age at presentation (p = 0.04). Ki-67 was weakly correlated with shorter survival after surgery (r = –0.103, p = 0.41). Partial resection strongest predicted recurrence (p < 0.001; OR = 13.0). Conclusion: Proliferative index does not change by location. Higher cell proliferation was seen in younger patients and associated with shorter time to and a higher risk of recurrence. Further study is needed to identify predictors for clinical behavior. Importance of Study: This study provides a detailed analysis of the proliferative indices of tumors arising from characteristic locations within the brain. With recent advances in our understanding of the differences in molecular and genetic profiles despite similar histologic diagnoses, we felt that it was important to review whether there were unique components of tumor behavior that could be identified. In turn, we sought to determine whether tumor behavior could be used to predict the clinical course. This knowledge is important, given that not every tumor may undergo complete surgical resection, and that some lesions may require more aggressive upfront adjuvant therapy or be closely monitored for recurrence. [ABSTRACT FROM AUTHOR]

We studied proliferative activity of multipotent mesenchymal stromal cells on collagen matrices containing platelets stabilized with silver nanoparticles. Dose-dependent stimulation of the growth of stromal cells without their structural damage was observed in the presence of stabilized platelets in proportion of 20-120 mln per 105 multipotent mesenchymal stromal cells. The same doses of non-stabilized platelets produced less pronounced stimulation effect. In higher doses (≥180 mln) stabilized platelets inhibited cell proliferation and induced their damage. Stabilized platelets enhanced migration of multipotent mesenchymal stromal cells; after formation of the monolayer, they actively colonized deep layer of the collagen matrix. The formed monolayer of multipotent mesenchymal stromal cells survived over 14 days without appreciable cell damage. [ABSTRACT FROM AUTHOR]

Neoadjuvant treatment discriminates responders, but pathologic complete response is uncommon in oestrogen receptor (ER)-positive/HER2-negative early breast cancer. We aimed to assess the prognostic value of Ki-67 index after neoadjuvant endocrine therapy (NET). We conducted a systematic literature search of PubMed, Embase, CENTRAL, and conference proceedings up to 22nd August 2023 to identify studies reporting the association of Ki-67 index after NET with recurrence-free survival (RFS) and/or overall survival (OS) in women with ER-positive/HER2-negative early breast cancer. We combined RFS and OS hazard ratios (HRs) with 95% confidence intervals (CIs). Twelve studies including 7897 patients were analysed. Most studies were clinical trials (n = 7547) including only postmenopausal women (n = 3953) treated with aromatase inhibitor (n = 3359). Three studies evaluated Ki-67 in a preplanned core biopsy at 2–4 weeks of NET (n = 3348), while nine evaluated Ki-67 in the surgical specimen (n = 4549) after 2–24 weeks of NET. Median follow-up ranged between 37 and 95 months for RFS and 62–84 months for OS. High Ki-67 index after NET was significantly associated with worse RFS (HR 2.48, 95% CI 1.86–3.30) and OS (HR 2.66, 95% CI 1.65–4.28). A sensitivity analysis including three studies that measured Ki-67 in a preplanned core biopsy showed similar association with RFS (HR 2.41, 95% CI 1.77–3.30). High Ki-67 after NET is associated with worse survival outcomes, even after a short course of NET, emphasising the prognostic value of this biomarker in women with ER-positive/HER2-negative early breast cancer. • Meta-analysis of Ki-67 prognostic value after neoadjuvant endocrine therapy. • Twelve studies reporting data from 7897 women with ER+/HER2− early breast cancer. • High Ki-67 was associated with worse recurrence-free survival and overall survival. • Ki-67 index after neoadjuvant endocrine therapy is a strong prognostic biomarker. • These findings will better inform clinical trials design and future clinical practice. [ABSTRACT FROM AUTHOR]

Background: Diseases of the prostate cause considerable morbidity and mortality in elderly population. There is limited literature regarding the prevalence of neoplastic and non-neoplastic lesions of prostate in rural Indian population. The current study attempts to document the occurrence of prostatitis, nodular hyperplasia (NH), prostatic intraepithelial neoplasia (PIN), prostate carcinoma (PCa) in patients operated at the study institution. Objective: To study the morphological spectrum of prostatic diseases. To correlate histopathological findings with serum prostate specific antigen (Sr.PSA) levels and evaluate the proliferative index by Ki-67 antibody in neoplastic and non-neoplastic lesions. Materials and Methods: Cross-sectional study comprising of 90 patients who underwent transurethral resection of prostate from January 2012 to June 2013. Routine tissue processing and immunohistochemistry with primary antibody Ki-67(Biogenex,USA) was performed to know the proliferative activity in all the cases. Statistical analysis was done by SPSS 11 software. Results: Out of 90 cases, 88.7% were benign and 12.3% malignant lesions. In 72 % of NH, 65.6% of Low grade PIN (LPIN), and 57.1% of HPIN the Sr PSA was in the range of 4.1-10 ng/ml. 81.8% of PCa had a PSA > 20ng/ml. The association between Sr PSA levels (>20ng/ml) and PCa was found to be highly significant. 62.8% of NH and 55.1% of LPIN had a PI between 2.1-25, whereas 71.2% of HPIN and 72.7% of PCa had higher index between 25.1-50. A significant association was found between the PI >25 and PCa. Multiple logistic regression suggest that Ki-67 acts as an independent parameter to indicate malignancy. Conclusion: NH comprised 48% of the total number of cases, followed by LPIN (32.3%) and HPIN (7.7%). Sr PSA is a reliable parameter to differentiate between benign and malignant diseases of prostate. PI bears a highly significant association with malignancy and is a independent parameter to indicate PCa.

Background. A significant problem of brain tumors diagnostics is the subjective histological criteria. A promising area of research is estimation of mitotic activity level, but counting mitotic figures can not be accurate in slides stained by hematoxylin and eosin and therefore immunohistochemical detection of expression Ki-67 is widely used. Despite considerable experience in using proliferative index, determined by using Ki-67-immunoreactivity, the technique requires further research for standardization and optimization. Objective. To determine the diagnostic value of the Ki-67 expression in astrocytomas. Methods. The study included 45 astrocytomas, which were received by biopsy or operation. Imunohistochemical determining of Ki-67-labeling was used for calculating of proliferation index. Statistical analysis was performed by nonparametric tests. Results. It was observed similar and relatively low levels of Ki-67 expression in astrocytoma Grade I and II (WHO), significantly lower than in groups III and IV levels. It was revealed significant differences between the results obtained by different researchers. Conclusion. The level of Ki-67 expression correlates with Grade of astrocytomas (p

Introduction: Dental diagnostic radiation is reported to cause significant damage in buccal cells while, the same effects due to Computed Tomography (CT) scans have not been routinely cited in literature. The buccal cells were studied in patients exposed to CT scans for evaluating the cells with micronuclei, associated nuclear abnormalities and changes in Proliferative Index (PI) of cells. The obtained head and neck CT scans i.e., CT for brain and facial bone, CT paranasal sinuses and CT cervical spine were compared in terms of the micronuclear counts. Aim: To estimate the counts of micronucleus associated nuclear abnormalities and changes in PI in patients before and after head and neck CT scans. Materials and Methods: An observational study, wherein 40 patients undergoing CT scans for head and neck region, were selected by consecutive systematic sampling. Buccal smears were made before and 10 days after CT scan. Papanicolaou (PAP) staining and micronuclear analysis were performed as per Tolbert’s criteria. The obtained cell counts were compared for differences before and after scans by paired t-tests. Results: Significant differences (p

BACKGROUND: Pediatric renal neoplasms comprise about 7%–8% of all neoplasms in children. Wilms tumour (WT) is the most common among pediatric renal tumours. AIMS AND OBJECTIVES: The study was undertaken to study the epidemiological occurrence of pediatric renal tumours in a tertiary care hospital and to ascertain the validity and reliability of touch smear imprint cytology in intraoperative diagnosis of renal tumours and correlate with subsequent histopathological diagnosis and to assess the expression of proliferation marker Ki-67 in different components and stages of WT. MATERIALS AND METHODS: It was a single-institution-based prospective and observational study, conducted for 2 years (from October 2013 to September 2015) in the department of pathology at our hospital. A total of fifty cases were enrolled in this study, all were below 15 years of age. RESULTS: Imprint cytology showed sensitivity, specificity, and diagnostic accuracy of 83%, 98%, and 95.74%, respectively, in diagnosing benign and malignant renal tumours. There was statistically significant correlation of imprint cytology with confirmatory histopathological examination of excision specimen (P < 0.001). Immunohistochemical analysis of Ki-67 was done in all WT cases. Epithelial component had higher proliferative index than blastemal component with P = 0.0082, which was highly statistically significant. CONCLUSION: Imprint cytology is found to be a less expensive, simple, and rapid method, which can be used as an adjunct to histopathology. Correlation between proliferation index as measured with Ki-67 antibody and tumour stage was found. Ki-67 is thus a relevant marker for assessing the proliferative activity. [ABSTRACT FROM AUTHOR]

Introduction: Dental diagnostic radiation is reported to cause significant damage in buccal cells while, the same effects due to Computed Tomography (CT) scans have not been routinely cited in literature. The buccal cells were studied in patients exposed to CT scans for evaluating the cells with micronuclei, associated nuclear abnormalities and changes in Proliferative Index (PI) of cells. The obtained head and neck CT scans i.e., CT for brain and facial bone, CT paranasal sinuses and CT cervical spine were compared in terms of the micronuclear counts. Aim: To estimate the counts of micronucleus associated nuclear abnormalities and changes in PI in patients before and after head and neck CT scans. Materials and Methods: An observational study, wherein 40 patients undergoing CT scans for head and neck region, were selected by consecutive systematic sampling. Buccal smears were made before and 10 days after CT scan. Papanicolaou (PAP) staining and micronuclear analysis were performed as per Tolbert's criteria. The obtained cell counts were compared for differences before and after scans by paired t-tests. Results: Significant differences (p<0.05; paired t-test) were noted between pre and post exposure values for head and neck CT scans in terms of Micronucleus (MN) counts, Binulceated cells (BN), Nuclear buds (NBUDs) and Multinucleated Micronucleus (MMN) cells. The post exposure radiation induced cell PI was found to be 6.0, a 3 fold rise from normal value of 2.0. Conclusion: CT scans taken for head and neck region caused changes related to DNA damage and genotoxicity in buccal mucosal cells. Comparatively, CT cervical spine have showed more nuclear abnormalities than CT for brain and facial bone and CT paranasal sinuses. The associated micronuclear cells have contributed to rise in PI. [ABSTRACT FROM AUTHOR]

Salivary carcinomas comprise 2-3 % of malignant tumors of the head and neck. The basic method of morphological study in early diagnostics is aspiration puncture with a fine needle (FNAB). Complex histologic structure and great diversity of morphological items complicate cytologic diagnostics of salivary tumors considerably. Immunocytochemical examination must be used to reduce the errors, it enables to reveal neoplastic cells at early stages of malignization. High proliferative activity of tumor cells is one of their biological peculiarities. Accuracy in differential diagnostics between benign and malignant tumors is improved through determination of mitotic index combined with a fine needle aspiration puncture.

Introduction: The Surface Epithelial Ovarian Carcinoma (SEOC) at the moment of diagnosis, the disease is extended beyond the structures of the pelvis. Ki-67 is one of the prognostic marker which determines the growth fraction of a tumour and its over expression is associated with malignancy, tumour aggression, reserved prognosis and metastasis. Aim: To evaluate the proliferative activity using Ki-67 immunostaining in SEOC and to correlate with histological subtype, grade, Federation of Gynecology and Obstetrics (FIGO) stage, CA125 levels for diagnostic and prognostic purpose. Materials and Methods: The study was conducted in JSS Medical College and Hospital, JSS University, Mysuru. It was a descriptive cross-sectional study involving 40 cases of SEOC over a period of two years. The proliferation expression related to Ki-67 antigen was evaluated by immunohistochemical monoclonal MIB-1 antibody. In each case, the Ki-67 labeling index (Ki-67 LI) was articulated as percentage of positively stained cells using high power objective of the microscope (x400). Results: Among the 40 carcinomas, 26 were serous, five mucinous, four each of clear cell and undifferentiated and one transitional cell carcinoma. A total of 75% were high grade tumours. High Ki-67 LI was associated with high grade tumours (69.9%), high grade serous tumours (65.34%) and advanced FIGO staging (70.6%) with the p-value of