In vivo cyclin E expression as a marker for early cervical neoplasia

Identification of human papillomavirus (HPV)-related early cervical neoplas ia and its distinction from benign epithelial alterations is based on eithe r subjectively applied morphologic criteria or on identification of associa ted papillomaviruses. The direct and indirect consequences of HPV infection , however, potentially include upregulation of some host genes. We investig ated one candidate, cyclin E, as a possible marker for HPV-related early sq uamous lesions. Serial paraffin sections from 92 archival cervical biopsy s pecimens were analyzed, including 19 non-neoplastic biopsy specimens, 30 lo w-grade and 31 high-grade squamous intraepithelial lesions (SILs), and 12 i nvasive carcinomas, Four parameters (histologic diagnosis, cyclin E stainin g, HPV status and, in selected cases, Ki-67 staining) were scored, and thei r relationship(s) were evaluated by the chi(2) independence test, Twenty-on e, 73, 79, and 75% of nonlesional epithelia, low-grade SILs, high-grade SIL s, and invasive squamous cell carcinomas, respectively, were HPV positive ( P < .001 for HPV status vs. diagnosis). Cyclin E staining was nuclear in di stribution, and the frequency of positive staining, i.e., moderate or stron g intensity, was significantly higher (P < .001 for cyclin E staining vs. d iagnosis) in all of the lesional epithelia (92.3, 51.6, and 50% of low-grad e and high-grade SILs and carcinomas, respectively) compared with nonlesion al epithelium (5.9%). Cyclin E positivity and/or HPV positivity was seen in 100% of the low-grade SILs, Epithelial Ki-GT and cyclin E staining were st rikingly different in frequency and distribution, Cyclin E was undetectable in basal cells of normal mucosa (which were positive for Ki-67) and limite d to suprabasal epithelium in noninvasive lesions, Cyclin E expression corr elates strongly with morphologic features of HPV-related preinvasive and in vasive cervical disease. This correlation is most pronounced in low-grade S ILs. The possibility that in vivo cyclin E staining is a generic marker for HPV infection in low-grade SILs merits additional study.