P16, Ki67 and P63 staining pattern in squamous metaplasia, CIN and cervical cancer

Abstract

Background: Persistent infection with Human Papilloma Virus (HPV) has been the main cause of squamous intra epithelial neoplasia which in turn leads to cancer. The incidence is 28.0%. Early identification of dysplasia and malignancy helps early intervention.Methods: To do Immunohistochemical staining using P16ink4a, Ki 67, and P63 in cervical squamous metaplasia, CIN I, II, III and correlate the H and E features with IHC patterns. Study was carried out in SRM Medical College Hospital and Research centre, Kattankulathur, Tamil Nadu, a descriptive study for a period of 2 years (2012 to 2014) on formalin fixed paraffin embedded tissues from cervix. H and E sections of uterine cervix were categorized into squamous metaplasia, CIN I, CIN II, CIN III and squamous cell carcinoma. 50 representative samples were subjected to Four-micrometer-thick sections and subjected to IHC using PathInsitu, using P16ink4a, Ki67 and P63. Statistics: Using SPSS for windows (V.17). Data expressed by number and percentage. Methods used were Chi square test, Screening test and ROC curve. Statistical significance was 0.05.Results: P63 has shown to be the best marker out of the three to distinguish the progression of a lesion towards dysplasia and malignancy in cervix. Ki 67 showed a specificity of 84.2% with a negative predictive value of 59.3%, and an ROC curve area of 69.2%. In this study, Ki67 showed lesser sensitivity than that of P63.Conclusions: P16 identifies HPV 16 infection in uterine cervix. Ki67 and P 63 are helpful in determining the nature of progression of lesion. High expression of Ki 67 indicates a neoplastic progression. P63 may be used to differentiate benign from malignant lesions. P16 with P63 showed good results in predicting the progression of a lesion.

P63 expression profile in uterine cervical lesions

“…The expression level of p63 (reflected in the mean IHC score) was exhibited in each studied groups (Group 1= reactive cervicitis, Group 2=CIN lesion, and Group 3 = cervical cancer cases). 7 This study was approved by the ethical commute of Hawler Medical University.…”

“…This emphasizes the role of p63 in cervical tumourigenesis, which is in parallel to other studies. 3,5,7 Finally, all cervical carcinomas other than SCC, including all adenocarcinomas cases and small cell carcinoma, were entirely negative for p63. Many previous studies agreed that p63 is useful as a powerful marker for squamous differentiation and, when diffusely expressed, excludes a glandular or neuroendocrine differentiation.…”

“…High P63 expression indicates a neoplastic progression. 7,8 Cervical intraepithelial neoplasia CIN is a dysplastic process in the cervical squamous epithelium and carries a risk of progression to cervical cancer; it is usually a long pre-invasive process, which over time can progress to invasive cervical carcinoma. 9 The WHO classification applied Low-grade Squamous Intraepithelial Lesion LSIL and High-grade Squamous Intraepithelial Lesion HSIL terminology to the previous classifications as CIN I, CIN II and CIN III based on the degree of dysplasia.…”

Expression of P16 biomarker in squamous cell carcinoma of uterine cervix and its association with clinico-pathological parameters: A cross-sectional study

“…Cervical cancer is the third most common cancer in women worldwide with a global prevalence of 11.7%, and accounts as the 5 th most common cause of cancerrelated deaths. Its annual estimated global incidence is 500,000 cases, with India accounting for approximately 100,000 cases [1][2][3] . Cervical cancer is the second common cancer in underdeveloped countries among females 1 .…”

“…Cervical cancer is the second common cancer in underdeveloped countries among females 1 . The Human Papilloma Virus (HPV) is a proven etiological factor 1,3,4 . The age range for cervical cancer is reported to be 27-80 years with mean age of 54.2 years; the maximum cases have been noted between 41-60 years of age 1 .…”