The importance of biological factors (bcl-2, bax, p53, PCNA, MI, HPV and angiogenesis) in invasive cervical cancer

Objective: The present study was designed to analyse the relationship betwe en apoptosis related proteins (bcl-2 and bax), tumour suppressor protein p5 3, proliferation markers (PCNA and mitotic index), human papillomavirus (HP V) and angiogenesis in cervical cancer and their impact on clinical outcome . Study Design: Tumours from 111 patients were assessed by immunohistochemi stry for the expression of bcl-2, bax, p53 and PCNA, by PCR for the presenc e of HPV-DNA, for the quantification of the mitotic index and the microvess el density (CD 31). The results were correlated with various histopathologi c characteristics and survival. Results: The multiple Cox's regression anal ysis for overall survival of all prognostic variables gave as best model: b cl-2 (P < 0.001), lymphovascular permeation (P = 0.004), mitotic index (P = 0.019), tumour grade (P = 0.048) and FIGO stage (P = 0.070). Subanalysis w as performed for the patients where the lymph node status was known (n = 79 ). Adding the lymph node status gave as best model for overall survival bcl -2 (P = 0.001), lymphovascular permeation (P = 0.003) and mitotic index (P = 0.044). However, they hardly influenced the association. Conclusion: In t he apoptotic pathway of cervical cancer, bcl-2 is one of most important pro teins. It can probably not only mediate cell death but also regulate cell g rowth. A better understanding of their relations will probably provide the basis for more rational cancer therapies in the future. (C) 2001 Elsevier S cience Ireland Ltd. All rights reserved.