Prognostic relevance of low-grade versus high-grade FIGO IB1 squamous cell uterine cervical carcinomas

e15529 Background: Ovarian cancer is one of the most lethal gynecologic malignancies and the leading cause of death among women with gynecological cancers. Different molecular markers have been studied for their prognostic relevance, but to date only CA 12-5 is used in routine diagnostic. Aberrant methylation of the estrogen receptor promoter (ESRp) was first described in colorectal cancer. Previous studies that described methylation of the ESRp in ovarian cancer suggested a potential role in cancer development. The aim of this study was to examine the methylation of the ESRp in a cohort of ovarian cancer patients in regard to its prognostic relevance. Methods: The study cohort consisted of 77 ovarian cancer patients that were diagnosed between 2000 and 2009 at the Department of OBGYN of the LMU Munich. A total of 50 patients died, 25 are still alive, 2 were lost to follow-up. Genomic DNA was isolated from paraffin-embedded cancer tissue and followed by bisulfite treatment. For detection of the methylated ESRp we used a sensitive real-time PCR. Results: Survival was significantly shorter for patients with aberrant promoter methylation within the subgroup of borderline, G1 and G2 tumors (31 patients; survival for methylated cases was 3.48 vs 4.91 years for unmethylated cases (p=0.010)). Within the small subgroup of borderline and G1 tumors (10 patients) survival for methylated cases was 4.73 vs 6.08 years for unmethylated cases (p=0.014). No significant difference of survival was observed for high grade (G3) ovarian cancer patients (p=0.745). Conclusions: We demonstrated for the first time that the methylation status of the ESRp might be a promising prognostic marker in ovarian cancer. ESRp methylation does not seem to be of prognostic relevance in high-grade ovarian cancer. In our study cohort a three-step grading system was used, but recent publications favor a two-step grading system. Thus, the G2 cases should be reevaluated to see whether they are G1 or G3. The difference in tumor etiology of low and high grade ovarian cancer might be responsible for the different prognostic relevance of ESRp methylation. Since our subgroup of borderline and G1 tumors is very small, these are preliminary results that have to be confirmed in a larger patient cohort.

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Useful histological findings in incisional biopsies of oral squamous cell carcinoma

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh1608384i ◽

2016 ◽

Vol 144 (7-8) ◽

pp. 384-390 ◽

Cited By ~ 1

Author(s):

Adna Ismerim ◽

Flávia Xavier ◽

Maria Cangussu ◽

Luciana Ramalho ◽

Ivan Agra ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Squamous Cell ◽

Granulation Tissue ◽

Vascular Invasion ◽

Giant Cells ◽

Tumor Thickness ◽

Low Grade ◽

High Grade ◽

Atypical Mitosis

Introduction. Oral squamous cell carcinoma (OSCC) is one of the most common head and neck cancers. Objective. The aim of this study was to investigate the histopathological features of OSCC specimens obtained from incisional biopsies and to alert clinicians to the importance of more representative biopsies. Methods.. Forty-eight OSCC samples were obtained from incisional biopsies and classified by Bryne?s score. The following morphological features were analyzed: invasive front, invasiveness, apoptotic cells, atypical mitosis, giant cells, acantholysis, ulceration, necrosis, calcification, surface epithelium, granulation tissue, desmoplasia, tissue invasions, inflammatory infiltrate and tumor thickness. Results. Ten (21%) cases were classified as high grade malignancies and 38 (79%) as low grade. Apoptotic cells (n = 26), atypical mitosis (1-2/20?; n = 38), giant cells (n = 8), acantholysis (n = 5), necrosis (n = 5), calcification (n = 1), granulation tissue (n = 32), desmoplasia (n = 4), perineural invasion (n = 2), muscular invasion (n = 8), invasion of salivary gland tissue (n = 3), vascular invasion (n = 10), and chronic inflammation (n = 33) were observed. Vascular invasion (p = 0.04, Pearson?s ?2 test) and necrosis (p = 0.04, Pearson?s ?2 test) were significantly associated with cases of high-grade malignant tumors. Atypical mitosis was associated with a greatest tumor thickness (p = 0.04, Fischer?s exact test). Conclusion. This study suggests that incisional biopsies may be useful and significant as they can show histopathological variables that are important to classify oral squamous cell carcinomas into low grade and high grade according to Bryne?s score, which was used in this study. Thus, more representative biopsies might be useful to achieve this and allow a more accurate planning.

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Immunohistochemical expression of p16INK4A in the lesions of uterine cervix

Annals of Pathology and Laboratory Medicine ◽

10.21276/apalm.2880 ◽

2020 ◽

Vol 7 (10) ◽

pp. A502-508

Author(s):

Niharika Rawat ◽

Shivapriya Rajan

Keyword(s):

Cervical Cancer ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Intraepithelial Neoplasia ◽

Low Grade ◽

High Grade ◽

Cervical Lesions ◽

Cancer Management ◽

Squamous Intraepithelial Neoplasia

Background: Cervical cancer is the major cause of cancer deaths among women. Globally, around 5,70,000 new cases of cervical cancer and 3,11,000 deaths occurred in the year 2018. In India, Cervical cancer is a leading cause of cancer related mortality among women and the number of deaths is 60,000 per year among 97,000 diagnosed patients, especially those from lower socioeconomic group. Human Papilloma Virus (HPV) plays a crucial role in causing cervical dysplasia. This is done by upregulating p16INK4A, a cyclin dependent kinase inhibitor through interaction with cellular regulatory proteins. Hence p16INK4A can be used as a biomarker, since it is directly related variable for the presence of HPV. This study was conducted to evaluate the expression of p16INK4A in benign, premalignant and malignant cervical lesions and to assess its utility in diagnosing and grading cervical lesions. Methods: A total of 80 cervical specimens categorized histopathologically into nonspecific cervicitis, low grade squamous intraepithelial neoplasia (LSIL), high grade squamous intraepithelial neoplasia (HSIL) and squamous cell carcinoma cervix were included in this prospective study of one-year duration. Immunohistochemical study of p16INK4A were interpreted qualitatively and semi-quantitatively by Allred scoring system (0 to 8 points) which measures the proportion of stained cells and intensity of staining of cells. The collected data were statistically analyzed by ANOVA and chi square test. Result: Qualitative method showed absence of p16INK4A expression in all nonspecific cervicitis. 16.7% (2/12) LSIL, 100% (12/12) HSIL and 100% (28/28) squamous cell carcinoma cases showed p16INK4A positivity. Allred scoring of p16INK4A showed 66% (8/12) HSIL and 85.7% (24/28) squamous cell carcinoma cases with score 3 positivity. Hence high-grade lesions showed higher expression of this marker. Conclusion: IHC expression of p16INK4A showed increasing degree of expression from benign to premalignant and malignant lesions suggesting its diagnostic and prognostic value in the cervical cancer management

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Precision in Gynecologic Cytologic Interpretation: A Study From the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology

Archives of Pathology & Laboratory Medicine ◽

10.5858/2003-127-1413-pigcia ◽

2003 ◽

Vol 127 (11) ◽

pp. 1413-1420 ◽

Cited By ~ 13

Author(s):

Andrew A. Renshaw ◽

Diane D. Davey ◽

George G. Birdsong ◽

Molly Walsh ◽

Patricia E. Styer ◽

...

Keyword(s):

Squamous Cell ◽

Educational Program ◽

Interlaboratory Comparison ◽

Squamous Cell Carcinomas ◽

Low Grade ◽

High Grade ◽

Exact Matching ◽

Exact Match ◽

High Degree ◽

Intraepithelial Lesions

Abstract Context.—Numerous studies address the accuracy or positive predictive value of cytologic interpretations for defined histopathologic entities. The reproducibility (precision) of cytologic interpretation is less well defined. Objective.—To establish and compare the reproducibility (precision) of cytologic interpretation in gynecologic cytopathology, as reflected in the educational program of the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology (PAP). Methods.—The pathologists' interpretations for both validated (25 745 responses) and educational conventional (14 353 responses) slides in the PAP program for 2001 were analyzed. The frequency of exact matches between the reference and pathologists' interpretation for each of the cytologic interpretative categories was identified, and the cumulative distributions of exact match rates were derived. χ2 Tests by reference interpretations were used for cytodiagnostic categories, least and most reproducible groupings, and high-grade (HSIL) versus low-grade (LSIL) squamous intraepithelial lesions. Results.—Pathologists' interpretations of negative, Candida, Trichomonas, herpes, and LSIL were characterized by a high degree of exact matching, while interpretations of repair, HSIL, adenocarcinoma, and squamous cell carcinomas were characterized by a lesser degree of exact matching (reproducibility). Pathologists' cytologic interpretations of HSIL were significantly less reproducible than those of LSIL. Conclusion.—The cytologic interpretations of the most significant categories (HSIL, squamous cell carcinoma, and adenocarcinoma) are less precise than those of specific infection (Candida, Trichomonas, and yeast), negative, and LSIL categories. Cytologic interpretations of LSIL are made with greater precision than those of HSIL and may represent a more appropriate endpoint to measure the precision performance of gynecologic cytology laboratories.

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Clinicopathologic and outcome features of superficial high-grade and deep low-grade squamous cell carcinomas of the penis

SpringerPlus ◽

10.1186/s40064-015-1035-2 ◽

2015 ◽

Vol 4 (1) ◽

Cited By ~ 3

Author(s):

Alcides Chaux

Keyword(s):

Squamous Cell ◽

Squamous Cell Carcinomas ◽

Low Grade ◽

High Grade

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Abstract LB-177: HPV16 CpG and de novo-cytosine methylation is differentially associated with low-grade versus high-grade anal intraepithelial neoplasia in HIV-infected men

10.1158/1538-7445.am2011-lb-177 ◽

2011 ◽

Author(s):

Dorothy J. Wiley ◽

Emmanuel V. Masongsong ◽

Provaboti Barman ◽

Mina Kalantari ◽

Hans Ullrich Bernard ◽

...

Keyword(s):

Cytosine Methylation ◽

De Novo ◽

Intraepithelial Neoplasia ◽

Anal Intraepithelial Neoplasia ◽

Low Grade ◽

High Grade ◽

Grade Versus

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Correlation of pathologic tumor grade with survival in oral cavity squamous cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e18557 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e18557-e18557

Author(s):

Eric Anderson ◽

Michael Luu ◽

Diana J. Lu ◽

Anthony Tuan Nguyen ◽

Jon Mallen-St. Clair ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Cavity ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Multivariable Analysis ◽

Tumor Grade ◽

Low Grade ◽

High Grade ◽

Intermediate Grade

e18557 Background: Pathologic tumor grade is a well-established prognostic risk factor that impacts staging and standard-of-care treatment decisions across multiple cancer types. However, the significance of tumor grade in cancers of the head and neck is less certain. Even in oral cavity squamous cell carcinoma (OCSCC), the head and neck cancer subsite with largest body of literature regarding the predictive value of tumor grade is, the prognostic significance of tumor grade remains controversial. Thus, we sought to better elucidate the prognostic importance of tumor grade in OCSCC. Methods: Patients with OCSCC diagnosed from 2004-2015 and undergoing primary surgery with or without adjuvant treatment in the National Cancer Data Base (NCDB) were identified. Overall survival (OS) was estimated using the Kaplan-Meier method with and without propensity score matching (PSM). Univariate and multivariable survival analyses were performed using Cox regression. Analyses were adjusted for multiple clinicopathologic factors, including age, sex, comorbidity status, year of diagnosis, pathologic staging, margin status, number of lymph nodes (LN) examined/positive, extranodal extension (ENE), lymphovascular invasion (LVI), adjuvant radiation, and concomitant chemotherapy. Results: Median follow-up was 40.7 months. Of 13,941 patients with OCSCC, 2,883 had low-grade tumors, 8,716 had intermediate-grade tumors, and 2,342 had high-grade tumors. Higher tumor grade was strongly associated with decreased survival. Specifically, five year OS was 62.7%, 52.8%, and 42.5% in low-grade (LG), intermediate-grade (IG), and high-grade (HG) OCSCC, respectively (p-value < 0.001). In PSM cohorts, OCSCC patients with high-grade had significantly worse 5 year OS (47.7% vs. 57.7%, p < 0.001) in comparison to those with LG OCSCC. Similarly, patients with IG tumors has worse 5-year OS (55.6% vs. 60.3%, p = 0.001) than patients with LG tumors in PSM cohorts. In multivariable analysis, both HG (HR 1.38, 95% CI 1.25-1.52, p < 0.001) and IG (HR 1.17, 95% CI 1.08-1.26, p < 0.001) OCSCC was associated with worse survival than what was observed in LG tumors. The magnitude of the independent effect of tumor grade in multivariable analysis was greater than or equal to what was observed with other well-established prognostic factors like margin positivity (HR 1.34), ENE (HR 1.35), and LVI (HR 1.18). Conclusions: Pathologic tumor grade is a strong predictor of survival among patients with OCSCC. Tumor grade should be considered when making therapeutic recommendations for OCSCC.

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