P16(INK4) stop expression and progression risk of low-grade intraepithelial neoplasia of the cervix uteri

The aim of the study was to evaluate the immunohistochemical expression of p16(INK4a) as a marker of progression risk in low-grade dysplastic lesions of the cervix uteri. p16(INK4a) immunohistochemistry was performed on 32 CIN1 with proven spontaneous regression of the lesion in the follow-up ( group A), 31 ( group B) with progression to CIN3 and 33 ( group C) that were randomly chosen irrespective of the natural history of the lesion. p16(INK4a) staining pattern was scored as negative ( less than 5% cells in the lower third of dysplastic epithelium stained), as focally positive ( less than or equal to 25%) and as diffuse positive (> 25%). A diffuse staining pattern was detected in 43.8% of CIN1 of group A, 74.2% of group B and 56.3% of group C. No p16(INK4a) staining was detected in 31.3% and 12.9% CIN1 lesions of groups A and B, respectively. Overall, 71.4% and 37.8% of p16(INK4a)-negative and diffusely positive CIN1 had regressed at follow-up, whereas 28.6% and 62.2% negative and diffusely positive CIN1 were progressed to CIN3, respectively (P< 0.05). All CIN3 lesions analyzed during follow-up of group B were diffusely stained for p16(INK4a). Although p16(INK4a) may be expressed in low-grade squamous lesions that undergo spontaneous regression, in this study, CIN1 cases with diffuse p16(INK4a) staining had a significantly higher tendency to progress to a high-grade lesion than p16(INK4a)-negative cases. p16(INK4a) may have the potential to support the interpretation of low-grade dysplastic lesions of the cervix uteri.