OVEREXPRESSION OF P185 IS NOT RELATED TO ERBB2 AMPLIFICATION IN OVARIAN-CANCER

Background: While in breast cancer the amplification and overexpressio n of the erbB2 gene has been reported in numerous studies and found to be correlated to poor prognosis, information about this oncogene with respect to ovarian cancer is still limited. A recent study reported t hat approximately 30% of tumor biopsies from ovarian cancer patients e xhibited erbB2 amplification and overexpression and suggested that the overexpression of this oncogene is an indicator of bad prognosis in o varian cancer. The purpose of our studies was to investigate amplifica tion of the erbB2 gene, the levels of erbB2 m-RNA and the erbB2 produc t (p 185) in ovarian cancer, and the correlation between these finding s and the pathological and clinical features. Results: Amplification o f the erbB2 gene was investigated by Southern blot analysis in 75 samp les from 62 patients; mRNA levels were evaluated by Northern blot anal ysis in 58 samples from 48 patients; and p185 was determined by immuno histochemistry in 65 samples from 65 patients. The erbB2 gene was ampl ified in only one case (1.6%), and a marked increase in erbB2 mRNA was found only in the same case. Staining for p185 was positive in 12 cas es (18.5%). The staining was always confined to the cytoplasm except i n the case that showed amplification of erbB2 in which p185 was locali zed in the membrane. No correlation was found between p185 positivity and pathological and clinical features or response to chemotherapy. We stern blot analysis showed that the molecular weight of p185 in positi ve ovarian cancer cells was approximately 10 KDa lower than in breast cancer. Conclusion: In contrast to breast cancer, in ovarian cancer th e amplification of erbB2 appears infrequent. The levels of p185 detect ed by immunohistochemistry were not related to the amplification of th e gene or to the increase in mRNA, suggesting the possibility of a lon ger half-life of the protein in the positive cases. The finding that e rbB2 product in ovarian cancer is mostly localised in cytoplasm and no t in the membrane as in breast cancer and that it has a lower molecula r weight than the p185 in breast cancer suggest that this oncogene pla ys a different biological role in these two neoplasms.