P16 as a diagnostic marker of cervical neoplasia: A tissue microarray study of 796 archival specimens

Abstract

Abstract. Background. To evaluate the usefulness of this biomarker in the diagnosis of cases of cervical neoplasia we studied the immunohistochemical expression of p16INK4ain a large series of archival cervical biopsies arranged into tissue microarray format. Methods. TMAs were constructed with tissue cores from archival formalin fixed, paraffin-embedded donor tissues from 796 patients, and included cases of cervical intraepithelial neoplasia (CIN)1 (n = 249), CIN2 (n = 233), CIN3 (n = 181), and invasive cervical carcinoma (n = 133). p16INK4aexpression was scored using two different protocols: 1) positive vs negative p16INK4astaining; 2) a semi-quantitative immunohistochemical score (0 to 8 points) according to the intensity of staining and the proportion of stained cells. Results. p16INK4Aexpression was not seen in normal cervix tissue, but was found with increasing frequency in the sequence: CIN1 (180/249; 72.3%) CIN2 (212/233; 91.0%) CIN3 (178/181; 98.3%) invasive carcinoma (131/133; 98.5%). Using semi-quantitative scoring, all normal cervical samples had low scores (from 0 to 2 points), whilst the number of specimens with high scores was proportional to the degree of cervical dysplasia or the presence of invasive carcinoma. Conclusion. Immunohistochemical analysis of p16INK4aexpression is a useful diagnostic tool. Expression is related to the degree of histological dysplasia, suggesting that it may have prognostic and predicative value in the management of cervical neoplasia. © 2009 Lesnikova et al; licensee BioMed Central Ltd.