Tumor hypoxia and expression of c-met in cervical cancer.
OBJECTIVE
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 pO(2) 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 (r=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.
Leo
Cornelia
C
Department of Gynecology, Leipzig University, Philipp-Rosenthal-Strasse 55, 04103 Leipzig, Germany. leo@medizin.uni-leipzig.de
Horn
Lars-Christian
LC
Einenkel
Jens
J
Hentschel
Bettina
B
Höckel
Michael
M
D000328:Adult; D000368:Aged; D001706:Biopsy; D015687:Cell Hypoxia / Q000502:physiology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000378:metabolism* / Q000473:pathology
C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases; D010100:Oxygen