Abstract
Morphological observations have indicated that there are two mechanisms in the human carcinogenesis: de novo carcinogenesis and multistep carcinogenesis through preneoplastic lesions. Recent molecular pathological techniques have made it possible to precisely analyze the step of the genetic event in the carcinogenetic process. Here, we report molecular pathological results suggesting multistep carcinogenesis in ovarian mucinous tumors. Specimens of 44 ovarian mucinous tumors, including 15 mucinous cystadenomas, 19 mucinous cystic tumors of borderline malignancy and 10 mucinous adenocarcinomas, were collected from our surgical files. Immunohistochemical analyses, including p53, Ki−67, p21/WAF1, cyclin D1 and c−erbB2, were performed. Loss of heterozygosity using 7 microsatellite markers and K−ras point mutation were examined. Furthermore, the correlation between the histological and genetic heterogeneities was analyzed. It was found that p53, Ki−67, and c−erbB2 expressions increased according to the histological grade as well as the frequency of genetic abnormalities. Histological heterogeneities were relatively well−correlated with the genetic heterogeneities. These results suggest that there is a subset of ovarian mucinous tumors in which there is an accumulation of genetic abnormalities.
