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Differential expression of cdk inhibitors p16, p21cip1, p27kip1, and cyclin E in cervical cytological smears prepared by the ThinPrep method

Our objective was to correlate p16, p21cip1, p27kip1, and cyclin E protein expression with the degree of dysplasia on ThinPrep Papanicolaou (Pap) smears using a modified immunoperoxidase staining. Smears read as normal, atypical squamous cells of undetermined significance (ASC‐US), low‐grade squamous intraepithelial lesion (LSIL), or high‐grade SIL (HSIL) were identified and tested for high‐risk human papillomavirus (HR‐HPV). Additional smears were processed for immunoperoxidase for p16, p21cip1, p27kip1, and cyclin E. Thirty‐four smears were satisfactory for study. The p16 was positive in all nine HSIL, in four of nine LSIL, and in one of seven ASC‐US. The p27kip1 was positive in all nine HSIL, in eight of nine LSIL, and in one of seven ASC‐US. The p21cip1 was positive in all nine HSIL, in one of nine LSIL, and in one of seven ASC‐US. Cyclin E was positive in seven of nine HSIL and in one of nine LSIL and in none of the ASC‐US smears. Normal smears were negative for all the antigens. There was poor correlation of protein expression and HR‐HPV infection. We concluded that p16, p21cip1, p27kip1, and cyclin E can be demonstrated on Pap smears and they are expressed differentially in dysplastic cells, with highest expression in HSIL. The p21cip1 and cyclin E showed the greatest correlation with HSIL. Diagn. Cytopathol. 2005;32:82–87. © 2005 Wiley‐Liss, Inc.