scholarly journals Immunohistochemical expression of p16INK4A in the lesions of uterine cervix

2020 ◽  
Vol 7 (10) ◽  
pp. A502-508
Author(s):  
Niharika Rawat ◽  
Shivapriya Rajan

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

2012 ◽  
Vol 136 (11) ◽  
pp. 1359-1365 ◽  
Author(s):  
Alfred Wellenhofer ◽  
Hermann Brustmann

Context.—Human telomerase reverse transcriptase (hTERT), an enzyme that enables cells to overcome replicative senescence and to divide indefinitely, is overexpressed in many cancers and their precursor lesions. Objective.—To test whether hTERT expression is related to neoplastic progression and resistance to apoptosis in vulvar epithelia. Design.—Immunoexpression of hTERT was evaluated in 101 formalin-fixed, paraffin-embedded archival vulvar epithelia consisting of normal squamous vulvar epithelia (n  =  25), lichen sclerosus (n  =  10), high-grade classic vulvar intraepithelial neoplasia (n  =  16), differentiated vulvar intraepithelial neoplasia (n  =  18), and vulvar invasive keratinizing squamous cell carcinoma (n  =  32) and related to survivin and p53 expression. Immunostaining for all factors was scored for moderate and strong intensities with regard to quantity to determine upregulation and overexpression (score 0, 0% immunoreactive cells; score 1+, <5% immunoreactive cells; score 2+, 5% to 50% immunoreactive cells; score 3+, >50% immunoreactive cells). Score 3+ was considered as overexpression. Results.—Nuclear hTERT immunoexpression was closely related to survivin reactivity, increased from normal vulvar squamous epithelia to lichen sclerosus and to high-grade classic vulvar intraepithelial neoplasia, differentiated vulvar intraepithelial neoplasia, and invasive keratinizing squamous cell carcinoma (P < .001), and followed the morphologic distribution of atypical squamous epithelial cells. Overexpression of hTERT was comparable to that seen for p53 in invasive keratinizing squamous cell carcinoma (P  =  .62); significant differences were calculated for differentiated vulvar intraepithelial neoplasia (P  =  .003) and high-grade classic vulvar intraepithelial neoplasia (P  =  .001). Conclusion.—Human telomerase reverse transcriptase is upregulated in vulvar intraepithelial neoplasia and invasive keratinizing squamous cell carcinoma compared with nonneoplastic squamous epithelia of the vulva as an apparently early and preinvasive event in the neoplastic transformation, with development of cellular longevity and resistance to apoptosis by survivin activation as associated features, independent of the etiology of vulvar intraepithelial neoplasia.


Author(s):  
Julia Wittenborn ◽  
Leonore Weikert ◽  
Birgit Hangarter ◽  
Elmar Stickeler ◽  
Jochen Maurer

Abstract An important issue in current oncological research is prevention as well as early detection of cancer. This includes also the difficulty to predict the progression of early or pre-cancerous lesions to invasive cancer. In this context, the characterization and categorization of pre-neoplastic lesions of squamous cell carcinoma [cervical intraepithelial neoplasia (CIN)] are an important task with major clinical impact. Screening programs are worldwide established with the aim to detect and eradicate such lesions with the potential to develop untreated into cervical cancer. From the literature it is known that around 5% of CIN 2 and 12% of CIN 3 cases will progress to cancer. The use of molecular markers extracted from cervical mucus might help to identify these high-risk cases and to exclude unnecessary biopsies or surgical treatment. Here we can show that micro RNA (miRNA) analysis from cervical mucus of 49 patients allowed us to distinguish between healthy patients and patients with CIN 3. The miRNA panel used in combination allowed for highly significant testing (P < 0.0001) of CIN 3 status. In parallel, the human papillomavirus status of the patients, the most important factor for the development of cervical cancer, significantly correlated with the miRNA markers hsa-miR-26b-5p, hsa-miR-191-5p and hsa-miR-143-3p, a subpanel of the original six miRNAs. We provide here a proof-of-concept for cervical mucus-based testing for pre-neoplastic stages of cervical squamous cell carcinoma.


2020 ◽  
Author(s):  
Yidi Liu ◽  
Huan Wu ◽  
Jingjiang Xu ◽  
Defu Chen ◽  
Hongyou Zhao ◽  
...  

Abstract Background: Cervical cancer is the fourth most common cancer in women. Early detection and diagnosis play an important role in secondary prevention of cervical cancer. This study aims to provide more information to develop an effective strategy for the prevention and control of cervical cancer in northern China. Methods: A retrospective single-centre descriptive cross-sectional study was conducted in Chinese PLA General Hospital located in Beijing, covering the period from January 2009 to June 2019. The patients who underwent a polymerase chain reaction (PCR)-based HPV genotyping test and cervical pathological diagnosis were included. Furthermore, we limited the interval between the two examination within 180 days for the purpose of making sure their correlation to analyse their relationship. Moreover, the relationship between different cervical lesions and age as well as single/multiple HPV infection was assessed.Results: A total of 3,134 patients were eligible in this study after HPV genotyping test and pathological diagnosis. Most of the patients (95%) were from northern China. Among the patients, 1,745(55.68%) had high-grade squamous intraepithelial neoplasia (HSIL), 1,354 (43.20%) had low-grade squamous intraepithelial neoplasia (LSIL) and 35 (1.12%) were Normal. The mean age was 42.06 ± 10.82(range, 17–79 years). The women aged 35-49 years accounted for the highest incidence rate. The top five most commonly identified HPV genotypes in each lesion class were as follows: HPV16, 58, 52, 31 and 51 in the class of HSIL; HPV16, 52, 58, 56 and 51 in the class of LSIL; HPV16, 31, 6,11, 52 and 58 in the class of normal. The frequencies of HPV single genotype infection and multiple genotypes infection were 55.26% and 34.18%, respectively. There was no difference in the attributable proportions of multiple genotypes infection amongst HSIL, LSIL and Normal.Conclusions: In Northern China, HPV16 was the most dominant genotype in the patients with pathological examination. The peak age of the onset of HSIL was between 35 and 49 years of age. Infection with multiple HPV genotypes did not increase the risk of HSIL. Type-specific HPV prevalence and attribution proportion to cervical precancerous lesions should be taken into consideration in the development of vaccines and strategy for screening in this population.


2021 ◽  
pp. jclinpath-2020-207302
Author(s):  
Alexander Reese ◽  
Curtis Edward Margo

Conjunctival squamous intraepithelial neoplasia (CSIN) represents the in situ precursor of squamous cell carcinoma. The graded severity of intraepithelial dysplasia is considered a measure of risk for progression to invasive carcinoma. The range of cytoarchitectural changes in CSIN overlaps those of reactive atypia, squamous epithelial papilloma and in situ sebaceous carcinoma. Pseudoepitheliomatous hyperplasia and benign hereditary dyskeratosis of the conjunctiva are conditions without risk of neoplastic transform that are potentially mistaken for CSIN.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18557-e18557
Author(s):  
Eric Anderson ◽  
Michael Luu ◽  
Diana J. Lu ◽  
Anthony Tuan Nguyen ◽  
Jon Mallen-St. Clair ◽  
...  

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.


Sign in / Sign up

Export Citation Format

Share Document