P16INK4A positivity in benign, premalignant and malignant cervical glandular lesions: a potential diagnostic problem

Abstract

A wide array of immunohistochemical markers have been evaluated with respect to their specificity in staining dysplastic cervical cells in cervical biopsies and cervical cytological smears. However, there is still a significant demand for better biomarkers to identify neoplastic cervical glandular and squamous epithelial cells precisely. The CDKN2A gene, located on chromosome 9p21, encodes the tumour suppressor protein, p16INK4A, which decelerates the cell cycle by inactivating CDK4 and CDK6. The aim of this study was to compare and contrast the expression pattern of p16INK4A in benign and neoplastic glandular lesions and tubo-endometrioid metaplasia. All cases in each category displayed some p16INK4A expression. Adenocarcinoma and in situ cases showed a combination of intense nuclear and cytoplasmic staining. It was observed that all cases of tubo-endometrioid metaplasia showed occasional nuclear positivity and definite cytoplasmic staining. These findings may have important implications for the potential utility of p16INK4A as a biomarker for glandular dysplastic lesions. While p16INK4A has been demonstrated to be an excellent marker of cervical dysplasia in squamous neoplastic lesions of the cervix, it has potential pitfalls in cervical glandular lesions that may limit the utility of this biomarker in resolving the nature of suspicious glandular lesions, particularly in cytopathology.

Immunophenotypic diversity of endometrial adenocarcinomas: implications for differential diagnosis

“…In gynecologic specimens, p16 immunohistochemistry has been used as an indirect assay for HPV infection 1,15,16 and an even more indirect method of determining the primary site of origin [1][2][3] (in human papillomavirus (HPV)-associated cervical cancers, viral oncoproteins E6 and E7 bind activated RB with consequent upregulation of p16 and promotion of DNA synthesis 15,17 ). Well-recognized problems with this approach have been published; p16 expression has been described in non-neoplastic ciliated cells, the cells of tuboendometrioid metaplasia 16,18,19 and even in endometrial cancer. 1,2,20 In endometrial cancer, the expression pattern is generally described as weak and patchy, in contrast to the strong immunoreaction typically encountered in endocervical adenocarcinomas of the usual type.…”

Evaluation Of P16, P27, Cycline D1, Bcl-2 Expressions In Uterine Cervical Intraepithelial Neoplasia and Skuamous Cell Carcinoma

“…İkişerli karşılaştırma testlerine göre, non-neoplazik/LSIL, non-neoplazik/HSIL, non-neoplazik/SHK grupların-da istatiksel olarak anlamlı ilişki bulundu. Önceki çalışmalarda P16'nın YR-HPV ve düşük riskli HPV ile enfekte serviks lezyonlarının ayırıcı tanısında, özellikle LSIL, skuamöz ve glanduler CIN tespit etmede son derece yararlı olduğu ve tarama proğram-larında kullanılabileceği, displazinin derecesini saptamada ve progresyonu öngörmede etkin olduğu bildirilmiştir (14)(15)(16) . P16 boyama ile ilgili sonuçlarımız önceki çalışmaların sonuçları ile benzer olup P16, özellikle LSIL'nun normal ya da reaktif değişiklikler-den ayrımında ve progresyonu öngörmede güvenilir bir belirteçtir.…”

Evaluation of a new p16INK4A ELISA test and a high‐risk HPV DNA test for cervical cancer screening: Results from proof‐of‐concept study

“…Degenerating endometrial cells have shown some staining for p16 INK4a . 11 Such cells might pose a source for false positive tests. In another study, Trichomonas vaginalis showed reactivity with some p16 INK4a antibodies.…”

“…Although glandular dysplasia and adenocarcinoma both can stain strongly for p16 INK4a , staining also occurs with benign cells showing tubal endometriod metaplasia. 11,13 Since sporadic p16 INK4a positivity has been noted in endometriod metaplasia and in some columnar cells, this may be another potential source for higher levels of p16 INK4a protein in lysed cervical specimens.…”