Comparison of p16 INK4a and ProEx™ C immunostaining on cervical ThinPrep® cytology and biopsy specimens

ProEx™ C and p16 INK4a staining of cytology/histology specimens have recently been explored to help distinguish high‐grade squamous intraepithelial lesions (HSIL) from benign mimics. The goal of this study was to evaluate the performance characteristics of p16 and ProEx C in tissue and patient matched ThinPrep® liquid‐based cytology specimens. Residual cervical ThinPrep cytology specimens and tissue blocks ( N = 64) from 63 patients were stained with p16 and ProEx C. Review of immunostained material, Papanicolaou and H&E stained slides was performed by two cytopathologists. The cytology slides were evaluated for the presence or absence of squamous atypia as well as immunoreactivity. Histologic specimens were interpreted as negative, indeterminate, or positive for each immunostain. There was 86% agreement (55/64) between the p16 and ProEx C stains on tissue specimens. Eleven specimens were interpreted as positive for both stains. All had a low‐ or high‐grade squamous lesion on the corresponding H&E section. ProEx C was able to identify four low‐grade squamous intraepithelial lesion specimens that were interpreted as negative by p16. All four HSIL specimens demonstrated p16 and ProEx C staining. However, 84% of cytology negative specimens demonstrated false‐positive staining. Clinical utilization of both stains, combined with morphologic features, may be beneficial for confirming HSIL on histologic specimens. ProEx C and/or p16 immunostains may lead to a false‐positive result in cytology specimens due to staining of normal appearing cells. Diagn. Cytopathol. 2010;38:564–572. 2009 Wiley‐Liss, Inc.