Expression of p16INK4a and cervical infection with high-risk human papillomavirus are not related to p53 activity in cervical intraepithelial neoplasia

Abstract

The objective of the study was to investigate the expression of p53 and p16(INK4a) in cervical intraepithelial neoplasia (CIN) and their relation with disease severity and high-risk human papillomavirus (HR-HPV) status. A series of 125 women with previous positive Pap smear were selected for this cross-sectional study. All patients underwent gynecological examination, including colposcopy. Specimens for Pap smears, Hybrid Capture 2 (HC2) test, and pathologic analysis were obtained. After evaluation of CIN grade, immunohistochemical detection of proteins p53 and p16(INK4a) was performed on paraffin-embedded sections. The extent of immunoexpression of both proteins was analyzed in relation to CIN grade and HR-HPV status. CIN was graded as 1 in 21, 2 in 17, and 3 in 87 specimens. p16(INK4a) positivity (at least 5% of epithelial cells stained) was found in 99 of 125 cases (79.2%) and was significantly higher in high-grade lesions as compared to low-grade CIN (P < 0.001). The expression of p53 did not differ across histologic strata. Protein expression neither of p16(INK4a) nor of p53 correlated with HR-HPV status. Expression of p16(INK4a) was not related with that of p53. Our study gives further support to previous findings of strong association of p16(INK4a) immunostaining with severity of epithelial atypia, but this protein may not be considered a predictor of HR-HPV status determined with HC2. By contrast, immunoexpression of p53 was related neither to CIN grade nor to HR-HPV status.

Detection and pathological value of papillomavirus DNA and p16INK4A and p53 protein expression in cervical intraepithelial neoplasia

“…The p53 oncoprotein expression has been detected in carcinomas from various sites, including breast, colon, bladder and lung. However, the correlation between HPV and p53 IHC staining in cervical lesions has been controversial (27,28). In the present study, no significant correlation was observed between p53 expression and cervical lesions.…”

“Immunocytochemical expression of P53, PTEN, FAS (CD95), P16INK4A and HPV L1 major capsid proteins in ThinPrep cervical samples with squamous intraepithelial lesions”

“…Several immunohistochemical studies on the expression of p53 in cervical intraepithelial lesions have been recently conducted and commonly report an increased frequency of p53 overexpression in HSIL as compared to LSIL . On the other hand there are also reports, albeit limited in number, suggesting that the levels of p53 overexpression may be higher in low grade lesions as compared to higher grade dysplasia or that there is no correlation whatsoever between p53 expression and intraepithelial disease grade . Significant discrepancies also exist with respect to the reported frequencies of p53 overexpression among LSIL or HSIL cases, respectively, as different studies report widely varied rates.…”

“…Several previous studies have investigated p53 protein expression in cervical intraepithelial lesions and in invasive carcinomas, but some of these results are contradictory . Furthermore, the published data on the expression of PTEN and Fas proteins in cervical intraepithelial neoplasia are rather limited, while, to the best of our knowledge, there are no previous immunocytochemical studies on the expression of these proteins in liquid‐based cervical smears.…”

The role of P16ink4a and P53 immunostaining in predicting recurrence of HG-CIN after conization treatment

“…Many recent studies have found the importance of p16 and p53 in cervical neoplasia 9,[12][13][14][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] . The vast majority rated the immunomarker positivity percentage for the presence of cervical intraepithelial neoplasia and correlated with the lesion severity 9,12,13,17,18,[21][22][23][24][25][26][27][28][29] . However, few studies related immune reaction with disease recurrence and/or prognosis 13.14-31 .…”

“…However, studies have failed to demonstrate different scores of p53 immunoreactivity in cervical intraepithelial neoplasia and cervical cancer. Conflicting results have also reported the relationship between p53 expression and progression of cervical intraepithelial neoplasia 12 .…”