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.