Effect of Human Papillomavirus on Cell Cycle–Related Proteins p16, Ki-67, Cyclin D1, p53, and ProEx C in Precursor Lesions of Cervical Carcinoma

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Abstract
In-depth study of cell cycle proteins and human papillomavirus (HPV) genotyping can provide useful information about the malignant potential of precursor lesions of cervical carcinoma (CC). Immunostaining of cell cycle–related proteins (p16, cyclin D1, Ki-67, p53, and ProEx C) was evaluated using tissue microarrays, and HPV genotypes were identified in 144 cervical tissue specimens encompassing normal or benign epithelial lesions, low- and high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively), and CC. In addition, 14 cases with atypical immature metaplasia (AIM) were included to compare their immunohistochemical features with those of well-established precursor lesions. Expression of p16, Ki-67, and ProEx C was most associated with the severity of dysplasia. Positive expression of p16, Ki-67, and ProEx C and negative expression of p53 seem to be related to HPV-16 infection. AIM cases show an immunohistochemical pattern more similar to LSIL than to HSIL. Immunohistochemical assessment of cell cycle proteins may help to distinguish normal and benign conditions of the cervix from precursor lesions of CC.