Impact of Cyclin D1 deregulation in HPV-mediated squamous intraepithelial lesions based on cell spots analysis.

Purpose: Human papillomavirus (HPV) involvement in cervical carcinogenesis represents a classical template of analyzing viral-mediated carcinogenesis. Our purpose was to investigate the role of abnormal cyclin D1 protein expression in HPV-mediated squamous intraepithelial lesions (SILs).
Methods: Eighty cases characterized as squamous intraepithelial lesions (SILs) and also borderline cases with molecularly proven HPV infection were examined. Using liquid-based cytology, we constructed 10 slides, each containing 8 cell spots. Immunocytochemistry (ICC) was performed using an anti-Cyclin D1 antibody. Digital image analysis was also implemented for evaluating objectively the protein expression levels on the corresponding stained slides.
Results: Cyclin D1 protein overexpression (moderate to high staining intensity values) was observed in 8/80 (10%) cell spots, whereas low expression rates were detected in 72/80 (90%) cases. Cyclin D1 overall expression was strongly associated with the HPV type group (HR-HPV) of the examined cases (p=0.001) and borderline with the cervical intraepithelial neoplasia (CIN) categorization (p=0.06). Concerning the influence of marker's protein expression in SIL cytological categorization, no statistical significance was identified (p=0.10).
Conclusions: Cyclin D1 overexpression is observed in a subset of SILs developed by HR-HPV persistent infection in cervical epithelial host cells. Although SIL and CIN categorization seem to be not influenced by cyclin D1 expression levels, mechanisms of gene's deregulation should be a promising molecular target for discriminating specific genetic signatures in the corresponding initial cervical neoplastic lesions.