p16(INK4a) immunocytochemistry in liquid-based cervical cytology: is it feasible for clinical use?

A consecutive series of 118 samples from patients referred to colposcopy assessment and follow-up with cytology and biopsies were analysed with immunocytochemical staining to determinate the expression of p16(INK4a). Accumulation of p16(INK4a) antigen has been proposed as a biomarker helpful for the identification of dysplastic cervical cells. In our study all benign cases were negative for p16(INK4a), while more than half of the high grade lesions showed moderate or strong reactivity. There was a correlation between CIN grade and p16(INK4a) expression levels with more advanced lesions showing stronger reactivity. The correlation between p16(INK4a) immunoreactivity and the severity of cytological abnormality was stronger, when the diagnosis was based on simultaneous routine cytology (p<0.001, chi(2) exact test for trend). There was no or weak reactivity in benign cases, as well as almost all low-grade lesions, while two thirds of high-grade lesions showed moderate or strong staining for p16(INK4a) antigen. Thus p16(INK4a) expression analysis yielded information which is consistent with results from the histopathology and is a simple way of emphasizing the presence of premalignant cell reactive atypias. This staining can be applied to cytological samples, and might be a complement prognostic procedure in order to find women at risk for cervical cancer.