The MET oncogene encodes the receptor for Hepatocyte Growth Factor/Scatter Factor, a unique growth factor that induces not only proliferation of epithelial cells, but also cell motility and invasiveness. DNA level and expression of the Met/HGF receptor gene were examined with Southern- and Western-blot analyses, respectively, in human ovary, benign ovarian tumors and epithelial ovarian carcinomas. The Met/HGF receptor was detectable in the surface epithelium of normal ovary. The level of expression was unchanged in benign ovarian tumors of various origins. Fourteen out of 67 malignant carcinomas (20%) showed a 3- to 10-fold increase in expression. In 5 additional cases the Met/HGF protein was overexpressed over 50-fold. This represents a total of 28% of cases. Overexpression was not associated with MET gene amplification. Overexpressing tumors belonged to different histotypic variants, but showed a well-differentiated phenotype. Clinically, overexpression was associated with disease at any pathologic stage, but was significantly correlated with premenopausal status of patients. These data suggest that expression of the Met/HGF receptor may add a selective growth advantage to a narrow subset of differentiated ovarian cancers in premenopausal patients.
In referral centers CHPP after optimal surgical debulking is a safe procedure for peritoneal carcinomatosis from colonic cancer. Locoregional control was obtained in the majority of the pretreated patients and 1-year survival was statistically improved. A closed abdomen CHPP procedure lasting 1 hour and standard mitomycin C at a dosage of 15 mg/m(2) is probably as efficacious as other hyperthermic procedures, using higher mitomycin C dosages, with a comparable or lower number of cases of side effects. These results, as in other published phase II studies, justify future randomized trials to assess definitively the role of CHPP in the treatment of locally advanced colon neoplasms in western countries.
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