Tumor hypoxia and expression of c-met in cervical cancer

Objectives. Hypoxia enhances malignant progression by promoting the development of metastases and increasing invasiveness. One key regulator that controls growth, invasion and metastasis in cancer cells is the growth factor receptor c-met. The aim of this study, therefore, was to investigate the expression of the c-met protooncogene in cervical cancers in relation to intratumoral hypoxia levels and to clinico-pathological parameters. Methods. 43 Patients with cervical cancer were subjected to intratumoral PO2 measurement with the Eppendorf electrode and biopsies were taken. The tissue was subsequently analyzed by immunohistochemistry with an anti-c-met antibody. Results. c-met was expressed in 72% of cervical cancers. There was a significantly stronger expression in poorly differentiated tumors (F=0.4, p=0.008). Furthermore, c-met expression was significantly associated with a spray-like pattern of invasion (P=0.008). However, there was no significant relationship between c-met expression and intratumoral hypoxia, pT stage, FIGO stage, lymphovascular space involvement, tumor size or overall survival. Conclusions. Although c-met has been shown to be hypoxia-induced in vitro, our results suggest that it is not the mediator of deleterious effects of hypoxia on clinical outcome in cervical cancer. (c) 2006 Elsevier Inc. All rights reserved.