The Role of Cyclins and Cyclin Inhibitors in the Multistep Process of HPV-Associated Cervical Carcinoma

الملخص EN

Background : Human papillomavirus (HPV) types 16 and 18 are associated with cervical carcinogenesis.

This is 5 possibly achieved through an interaction between HPV oncogenic proteins and some cell cycle regulatory genes.

However, the exact pathogenetic mechanisms are not well defined yet.

Methods : We investigated 110 subjects (43 invasive squamous cell carcinoma (ISCC), 38 CIN III, 11 C1N II, 18 CIN I) confirmed lo be positive Tor HPV16 and / or 18 as well as 20 normal cervical tissue (NCT) samples for abnormal expression of cyclin DL, cyclin E.

CDK4, cyclin inhibitors {p2Dwaff, p27, pl6lNK4A) and Ki-67 using im-munohistochcmistry and differential PCR techniques.

Remits : There was a significant increase in the ex-pression of Ki-67, cyclin E, CDK4, pl6lNK4A (p = 0.003, 0.001, 0.001) and a significant decrease in p27KIPIPI from NCT to ISCC (P = 0.003).

There was a significant correlation between altered expression of p27KIPI and pl6INK4A (p < 0.00l), cyclin Dl and CDK4 (P = 0.001), cyclin E and p27IPLK(p = 0.011) in all studied groups.

In ISCC, there was signilkanl relationship between standard clinicopalho-logical prognostic factors and high Ki-67 index, increased cyclin Dl and cyclin E, reducedp27KIP1 and p2lwaf.

Conclusion : 1) Aberrations involving p27KIPI cyclin E, CDK4 and p / 6INK4A are considered early events in HPV 16 and 18-associated cervical carcinogenesis (CINI & II), whereas cyclin Dl aberrations are laic events (CIN111 & ISCC).

2) Immunohistochemical tests for pl6INK4A and cyclin E could help in early diagnosis of cervical carcinoma.

3) Only F1GO stage, cyclin DL p27KIPIand Ki-67 arc independent prognostic factors that might help in predicting outcome of cervical cancer patients.