Objective: To investigate the patterns of expression of key cell cycle proteins targeting on the human papillomavirus (HPV) sites E6 and E7 in cervical carcinoma.
Methods: Semiquantitative immunohistochemistry was used to determine the expression of the cell cycle regulatory factor p53, retinoblastoma gene product pRb, cyclin-dependent kinase inhibitors p21(CIP1/WAF1) (p21), p16(INK4A) (p21), and p27(KIP1) (p21), and cyclin D1 targeting on the HPV sites E6 and E7 in 73 HPV 16-positive specimens of cervical squamous cell carcinoma, 35 from Australia patients and 38 age, lymph node status, and grade of tumor-matched Chinese patients.
Results: There were no significant differences in age, lymph node status, and grade of tumor between the Chinese and Australian groups, however, the number of the patients in advanced stage (>Stage IIa) was greater in the Chinese group than in the Australian group (19:7). The positive rate of p53 in the Australian group was 3%, significantly lower than that in the Chinese group (23%, P = 0.028). The upregulation rate of pRb, p21, and p27 in the Australian group were 56%, 63% and 34% respectively, all significantly higher than those in the Chinese group (89%, 97%, and 89% respectively, P = 0.01, P < 0.001, and P < 0.001). There were no significant differences in the upregulation rate of p16 and cyclin D1 expression rate between the Australian group and Chinese group (97% versus 100%, and 3% versus 12%, both P > 0.05). In the combined data of both groups, the positive rate of p53 was 13%; and the upregulation rates of pRb, p16, p21, p27, and cyclin D1 were 74%, 99%, 81%, 63% and 7% respectively.
Conclusion: Cervical carcinoma overexpresses pRb, p16, p21, and p27. Tumors from Chinese patients are significantly more likely to be positive in p53 and to have upregulated pRb, p21, and p27 than their Australian counterparts. The molecular pathways to human papillomavirus-induced cervical cancer may be influenced by ethnicity and further investigation is necessary.