Immunohistochemical Expression of p16^INK4a and bcl-2 According to HPV Type and to the Progression of Cervical Squamous Intraepithelial Lesions

Abstract

S U M M A R YInactivation of the cell cycle inhibitor gene p16MTS1 seems to be involved in human papillomavirus (HPV)-related carcinogenesis because E6 and E7 oncoproteins may impair p16 INK4a and, indirectly, bcl-2 functions. In this study, we analyzed the role of immunohistochemical expression of p16 INK4a and bcl-2 in HPV-infected cervical biopsies as prognostic markers of the progression of squamous intraepithelial lesion (SIL). Sixty-five cervical biopsies were stratified into two subgroups according to the second biopsy: 27 of them maintained a low-grade (LG)-SIL diagnosis, and 38 progressed from LG-SIL to high-grade (HG)-SIL. p16 INK4a and bcl-2 quantitative expression levels were measured by the immunoperoxidase method. PCR-DNA techniques were used to detect and type HPV. The Wilcoxon and Fisher exact tests were employed for the statistical analysis. In the group with an LG-SIL diagnosis at the second biopsy, no significant associations were found between p16 INK4a and bcl-2 expression and presence of HPV16/18. In the group that progressed to HG-SIL, a significant association was observed between p16 INK4a overexpression and HPV16/18 presence ( p ϭ 0.021), but none with bcl-2 levels. It is concluded that immunohistochemical bcl-2 expression may not be useful for predicting the progression of HPV-related SIL. In contrast, p16 INK4a overexpression seemed to be associated with HPV 16 and 18, suggesting that it may be a good marker for predicting SIL progression.

Immunohistochemical expression of p16INK4a is predictive of HR-HPV infection in cervical low-grade lesions

“…9,13,17 The present study aimed at evaluating p16 overexpression in parallel with HPV infection, in a series of 100 cervical biopsies comprising normal tissues, preneoplastic and neoplastic lesions. The potential association between p16 and HPV infection was investigated to verify whether p16 upregulation could be a valuable tool in the identification of dysplastic lesions caused by HR-HPV genotypes.…”

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

“…Bcl-2 ile yapılan çalışmalarda farklı sonuçlar bildirilmiş olup bulgularımız bunların bir kısmı ile uyumludur. LSIL'da güçlü boyanma olduğu, bunlardan HSIL'a ilerleyen lezyonlarda boyanmanın azaldığı (22) , CIN'lerde lezyon derecesi yükseldikçe boyanmanın arttığı, SHK'de ise boyan-ma kaybı (23) yanı sıra aksini ileri süren sonuçlarda bildirilmiştir (24) . Servikal lezyonların ayrımında Bcl-2, p16 gibi diğer belirteçler ile birlikte kullanılır-sa ayrıcı tanıda yardımcı olabilir, ancak tek başına kullanımı uygun değildir.…”

The Indicators of Predicting Disease Outcome in HPV Carcinogenesis

“…Guimarães et al, (2005) found by immunohistochemical techniques that expression of Bcl2 in HPV-infected cervical biopsies is not useful for predicting the progression of HPV-related SIL. On the other hand, Singh et al, (2009) noted cytoplasmic expression of Bcl2 protein in cervical dysplasia, a various intensity of immunoreactivity between different cytological grades of cervical smears and an association with the presence of HPV16/HPV18.…”