scholarly journals Expression of p53, p63, podoplanin and Ki-67 in recurring versus non-recurring oral leukoplakia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jonas Sundberg ◽  
Sushma Pandey ◽  
Daniel Giglio ◽  
Erik Holmberg ◽  
Göran Kjeller ◽  
...  
Keyword(s):  
Cox Regression ◽  
Prognostic Significance ◽  
Recurrence Risk ◽  
Oral Leukoplakia ◽  
Surgical Removal ◽  
Ki 67 ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Potentially Malignant ◽  
A Prospective Study

AbstractOral leukoplakia (OL), a potentially malignant disorder, recurs in 40% of cases after surgical removal. Recurrence is a risk factor for malignant transformation. We aimed to examine the prognostic significance of four biomarkers related to cell proliferation: p53, p63, podoplanin (PDPN) and Ki-67 in predicting recurrence. Formalin-fixed-paraffin-embedded specimens from excised OL (n = 73, 33 recurrent; 40 non-recurrent) were collected in a prospective study. Immunohistochemistry was used to visualise expression of p53, p63, PDPN and Ki-67. Image analysis software was used for quantification of p53-, p63- and Ki-67-expressing cells, while PDPN was analysed visually. The expression of all four proteins were higher in recurrent compared with non-recurrent OL, only expression of p53 was statistically significant. In uni- and multivariable Cox regression analyses of individual markers, expression of p63 was significantly associated with higher recurrence risk (p = 0.047). OL with a combined high expression of both p53 and p63 had a significantly higher risk to recur [Log Rank, p = 0.036; multivariate Cox, HR: 2.48 (1.13–5.44; p = 0.024)]. Combination of p53 and p63 expression may be used as a prognostic biomarker for recurrence of OL.

scholarly journals TERT promoter mutations in penile squamous cell carcinoma: high frequency in non-HPV-related type and association with favorable clinicopathologic features

2021 ◽  
Vol 147 (4) ◽  
pp. 1125-1135
Author(s):  
Sang Kyum Kim ◽  
Jang-Hee Kim ◽  
Jae Ho Han ◽  
Nam Hoon Cho ◽  
Se Joong Kim ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Malignant Neoplasm ◽  
Clinicopathologic Features ◽  
Ki 67 ◽  
Tissue Samples ◽  
Formalin Fixed Paraffin ◽  
Tert Promoter Mutations ◽  
Formalin Fixed Paraffin Embedded ◽  
Penile Squamous Cell Carcinoma ◽  
Promoter Mutations

Abstract Purpose Penile carcinoma is a rare malignant neoplasm with a largely unknown molecular pathogenesis. Telomerase reverse transcriptase promoter (TERT-p) mutations have been detected in several types of human malignancies. The aim of this study was to investigate the presence of TERT-p mutations in penile squamous cell carcinomas (SCCs) and their associations with clinicopathologic features. Methods In this retrospective study, Sanger sequencing was performed to detect TERT-p mutations in formalin-fixed paraffin-embedded tissue samples from 37 patients with penile SCC, 16 patients with cutaneous SCC, and 4 patients with non-neoplastic penile/skin tissue. The expression of p16INK4a and Ki-67 was investigated via immunohistochemistry. Associations of TERT-p mutation with clinicopathological factors, immunohistochemical results, and clinical outcome were statistically analyzed. Results Recurrent TERT-p mutations were identified in 18 out of 37 (48.6%) penile SCCs, including all 3 carcinoma in situ cases. TERT-p mutations were significantly more frequent in non-human papilloma virus (HPV)-related penile SCC types than in non-HPV-related penile SCC based on both histologic classification and p16INK4a immunoreactivity. Furthermore, TERT-p mutation was associated with a low histologic grade, low mitotic count, absence of necrosis, low Ki-67/MIB-1 labeling index, and absence of lymph node or distant metastasis. Conclusion Our study shows TERT-p mutations are the most frequent somatic mutations in penile SCC. In addition, TERT-p mutations are far more frequent in non-HPV-related penile SCC than in HPV-related penile SCC, indicating TERT-p mutations may have a role in tumorigenesis distinct from HPV-related penile SCC.

Expression of proliferation genes in formalin-fixed paraffin-embedded (FFPE) tissue from breast carcinomas. Feasibility and relevance for a routine histopathology laboratory

2016 ◽  
Vol 70 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Carla Thomas ◽  
Cleo Robinson ◽  
Ben Dessauvagie ◽  
Benjamin Wood ◽  
Greg Sterrett ◽  
...  
Keyword(s):  
Gene Expression ◽  
Breast Carcinoma ◽  
Expression Profiling ◽  
Proliferative Activity ◽  
Breast Cancers ◽  
Breast Carcinomas ◽  
Ki 67 ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

AimBreast carcinoma proliferative activity, histological grade and commercial molecular tests are all important in prognostication and treatment. There is a particular need for improved, standardised techniques for subclassification of grade 2 breast cancers into low-risk and high-risk prognostic groups. In this study we investigated whether gene expression profiling of five proliferation genes was feasible using breast cancer tissue in a clinical setting and whether these profiles could enhance pathological assessment.MethodsExpression of five proliferation gene mRNAs; Ki-67, STK 15, CCNB1, CCND1 and MYBL2, was quantified in 27 breast carcinomas and compared with Ki-67 proliferation index (PI) and Nottingham mitotic score.ResultsExpression of Ki-67, STK15 and MYBL2 mRNA showed moderate Spearman's correlation with Ki-67 PI (p<0.01), but CCND1 and CCNB1 showed weak, non-significant correlation. Individual gene expression did not associate with mitotic score but combined mRNA expression correlated with both Ki-67 PI (p=0.018) and mitotic score (p=0.03; 0.007).ConclusionsThis study confirms mRNA analysis in breast carcinoma formalin-fixed, paraffin-embedded samples is feasible and suggests gene expression profiling, using a small set of five proliferation genes, has potential in aiding histological grading or assessment of proliferative activity of breast cancers. To fully evaluate the clinical applicability of this approach, a larger cohort study with long-term follow-up data is required.

Antitumor immune response is associated with favorable survival in GEP-NEN G3

2021 ◽  
Vol 28 (10) ◽  
pp. 683-693
Author(s):  
Vivian Rosery ◽  
Henning Reis ◽  
Konstantinos Savvatakis ◽  
Bernd Kowall ◽  
Martin Stuschke ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cell ◽  
Spatial Interaction ◽  
Antitumor Immune Response ◽  
Cytotoxic T Cell ◽  
Neuroendocrine Neoplasms ◽  
Ki 67 ◽  
Tissue Samples ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded

The tumor immune microenvironment (TME) represents a key determinant for responses to cancer treatment. However, the immune phenotype of highly proliferative gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) is still largely elusive. In this retrospective study, we characterized the TME of high-grade (G3, Ki-67 > 20%) GEP-NEN. We analyzed formalin-fixed paraffin-embedded samples from 37 patients with GEP-NEN G3 by immunohistochemistry and multiplex immunofluorescence to address the abundance and spatial interaction of relevant immune subsets. We focused on the expression of immune checkpoint molecules PD-1 and PD-L1, the cytotoxic T-cell marker CD8, and the tumor-associated macrophage marker CD206. Findings were correlated with overall survival (OS) from the date of a cancer diagnosis. Patients with PD-L1-positive tumors (CPS ≥ 1) and intense PD-1+CD8+ immune cell infiltration showed the most favorable median OS. Multiplex immunofluorescence staining of ten representative tissue samples illustrated intratumoral heterogeneity of PD-L1 expression. Dense PD-1+CD8+ immune cell infiltrates were observed in PD-L1-positive tumor regions but not in PD-L1-negative regions. Proximity analysis revealed a spatial interaction between PD-1+CD8+ cells and PD-L1-positive cells. Our data suggest a pre-existing antitumor immune response in the TME in a subgroup of GEP-NEN G3. This supports a targeted clinical exploration of immunotherapeutic approaches.

Tumor-associated immune cells and progression-free survival in advanced endometrial cancer (EC), results from the PHAEDRA trial (ANZGOG 1601).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5584-5584
Author(s):  
Deborah Smith ◽  
Kristy Robledo ◽  
Sonia Yip ◽  
Michelle Cummins ◽  
Peey-Sei Kok ◽  
...  
Keyword(s):  
Immune Cells ◽  
Predictive Value ◽  
Tumor Response ◽  
External Validation ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Immune Biomarkers ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
The Individual

5584 Background: Activity of durvalumab in patients with deficient mismatch repair (dMMR) advanced endometrial carcinoma (EC) was confirmed in the PHAEDRA trial (ANZGOG 1601). This study investigated the association between immune biomarkers and clinical outcomes in PHAEDRA. Methods: Formalin-fixed paraffin embedded sections immunohistochemically stained for PD-L1 using the Ventana platform, were with matched H&E slides scored independently by two pathologists according to the Ventana PD-L1 (SP263) algorithm for urothelial carcinoma (UC). Immune biomarkers assessed were PD-L1 staining of tumor cells (TCP) and immune cells (IC), and presence of tumor-associated immune cells (ICP). Results: Sixty-seven of the 71 patients had sufficient tumor for PD-L1 testing. AUC were 0.667, 0.726 and 0.644 for TCP, ICP and IC, respectively for predicting tumor response. Optimal cutpoints were TCP≥1%, ICP≥10% and IC≥35%. ICP≥10% achieved the highest sensitivity (53%) and specificity (82%) of the individual cutpoints. The optimal cutpoint algorithm was able to identify patients who would not respond, (sensitivity 88%, negative predictive value 92%), but had low specificity (48%) and positive predictive value (37%). Differences in PFS were found using ICP≥10% (logrank p = 0.01), compared to TCP (p = 0.25), IC (p = 0.48) and the UC algorithm (p = 0.08) (Figure 1). PFS was shorter in patients with pMMR than dMMR after adjusting for ICP (HR 2.99, 95%CI: 1.61-5.57, p < 0.001). Adjustment for MMR reduced the prognostic significance of ICP≥10% for PFS (HR 0.59, 95% CI: 0.28-1.23, p = 0.16). For OS, differences were seen for the UC algorithm (p = 0.02), but not ICP (p = 0.07), TCP (p = 0.18) or IC (p = 0.23). Similarly to PFS, adjustment for MMR reduced the prognostic significance of the UC algorithm for OS (HR: 0.53, 95% CI: 0.25-1.12, p = 0.10). Conclusions: In this exploratory analysis, ICP was more closely associated with tumor response and PFS than TCP or IC. ICP alone was better than the UC algorithm for predicting PFS. The optimum cutpoint algorithm was promising for identifying non-responders, but requires external validation. Clinical trial information: ACTRN12617000106336.

Quantitative immunohistochemical (IHC) assessment of ataxia-telangiectasia mutated (ATM) in estrogen receptor (ER) negative early breast cancer (BC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21083-e21083
Author(s):  
Patricia Tang ◽  
Alexander C. Klimowicz ◽  
Gregory Russell Pond ◽  
Daniel Yick Chin Heng ◽  
Marc A. Webster ◽  
...  
Keyword(s):  
Cellular Response ◽  
Cox Regression ◽  
Stage I ◽  
Ataxia Telangiectasia Mutated ◽  
Expression Ratio ◽  
Regression Methods ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
The Impact ◽  
Quantitative Fluorescence

e21083 Background: ATM plays a key role in the cellular response to DNA damage and germline mutations are associated with a predisposition to BC. We evaluated the impact of ATM expression on outcomes in Stage I-III ER negative BC patients (pts). Methods: A tissue microarray was constructed from formalin-fixed paraffin-embedded specimens of ER negative Stage I-III BC pts from the Tom Baker Cancer Centre. ATM expression was assessed by quantitative fluorescence IHC using a rabbit anti-ATM monoclonal antibody (Epitomics) and the HistoRx AQUA platform. ATM expression index (EI) was calculated by the tumor cell to stroma expression ratio. Prognostic ability of ATM EI was explored univariately, and multivariately after adjusting for clinicopathological factors selected using algorithmic methods, with Cox regression methods. Results: Of 126 eligible pts treated from 1999-2004, 44.4% were HER2-neu + and 52.4% were triple negative. ATM EI was normalized using a logarithmic transformation. Univariately, higher ATM EI was associated with worse outcomes (Table). Multivariately, higher ATM EI remained significantly prognostic for recurrence-free survival (RFS) (HR=5.46, p=0.046), local RFS (HR=5.56, p=0.052), distant RFS (HR=4.38, p=0.080), but not overall survival (p=0.48). Conclusions: High ATM EI is associated with worse RFS in ER negative BC in this hypothesis-generating study. Validation of this finding is currently ongoing. [Table: see text]

Glioblastoma Contains Topologically Distinct Proliferative and Metabolically Defined Subpopulations of Nestin- and Glut1-Expressing Cells

2021 ◽  
Author(s):  
Michael Prosniak ◽  
Lawrence C Kenyon ◽  
D Craig Hooper
Keyword(s):  
Glucose Transporter ◽  
Intermediate Filament Protein ◽  
Protein Markers ◽  
Ki 67 ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Hematoxylin And Eosin ◽  
Glial Lineage ◽  
Filament Protein ◽  
Von Willebrand

Abstract The difficulty in treatment of glioblastoma is a consequence of its natural infiltrative growth and the existence of a population of therapy-resistant glioma cells that contribute to growth and recurrence. To identify cells more likely to have these properties, we examined the expression in tumor specimens of several protein markers important for glioma progression including the intermediate filament protein, Nestin (NES), a glucose transporter (Glut1/SLC2A1), the glial lineage marker, glial fibrillary acidic protein, and the proliferative indicator, Ki-67. We also examined the expression of von Willebrand factor, a marker for endothelial cells as well as the macrophage/myeloid markers CD163 and CD15. Using a multicolor immunofluorescence and hematoxylin and eosin staining approach with archival formalin-fixed, paraffin embedded tissue from primary, recurrent, and autopsy IDH1 wildtype specimens combined with high-resolution tissue image analysis, we have identified highly proliferative NES(+)/Glut1(–) cells that are preferentially perivascular. In contrast, Glut1(+)/NES(–) cells are distant from blood vessels, show low proliferation, and are preferentially located at the borders of pseudopalisading necrosis. We hypothesize that Glut1(+)/NES(–) cells would be naturally resistant to conventional chemotherapy and radiation due to their low proliferative capacity and may act as a reservoir for tumor recurrence.

M30 Expression Demonstrates Apoptotic Cells, Correlates With In Situ End-Labeling, and Is Associated With Ki-67 Expression in Large Intestinal Neoplasms

2000 ◽  
Vol 124 (12) ◽  
pp. 1768-1772 ◽  
Author(s):  
Norman John Carr
Keyword(s):  
Regression Line ◽  
Strong Positive Correlation ◽  
Strongly Correlated ◽  
Ki 67 ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Secondary Objective ◽  
Formalin Fixed ◽  
Number Of Cells

Abstract Context.—The monoclonal antibody M30 recognizes a neoepitope of cytokeratin 18 produced during apoptosis. It is reactive in formalin-fixed, paraffin-embedded tissue and has great potential in the study of apoptosis in clinical and experimental material. Objectives.—To compare the results of M30 immunoexpression with a more established technique of demonstrating apoptosis in tissue sections, in situ end-labeling. A secondary objective was to compare the results with immunoexpression of the proliferation-associated antigen Ki-67. Design.—Retrospective analysis of adenomas and adenocarcinomas of the large intestine. Interventions.—Immunohistochemistry for M30 and Ki-67, and in situ end-labeling. Formalin-fixed, paraffin-embedded tissue was used. Main Outcome Measures.—The number of cells positive for M30, Ki-67, and in situ end-labeling, expressed as a proportion of the total number of cells counted. Results.—A strong positive correlation was found between in situ end-labeling and expression of M30, although the counts were widely scattered around the regression line. Counts of Ki-67 were strongly correlated with both M30 expression and in situ end-labeling. Immunoexpression of M30 was generally easier to interpret than in situ end-labeling, and the procedures for M30 immunohistochemistry were technically less exacting. Conclusion.—These findings support the application of M30 immunoreactivity in the study of apoptosis.

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