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Open Access Highly Accessed Research

p16 as a diagnostic marker of cervical neoplasia: a tissue microarray study of 796 archival specimens

Iana Lesnikova1*, Marianne Lidang2, Stephen Hamilton-Dutoit1 and Jørn Koch1

Author Affiliations

1 Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark

2 Institute of Pathology, Herlev Hospital, Herlev, Denmark

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Diagnostic Pathology 2009, 4:22  doi:10.1186/1746-1596-4-22

Published: 9 July 2009

Abstract

Background

To evaluate the usefulness of this biomarker in the diagnosis of cases of cervical neoplasia we studied the immunohistochemical expression of p16INK4a in 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). p16INK4a expression was scored using two different protocols: 1) positive vs negative p16INK4a staining; 2) a semi-quantitative immunohistochemical score (0 to 8 points) according to the intensity of staining and the proportion of stained cells

Results

p16INK4A expression 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 p16INK4a expression 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.