Survivin, bcl-2 and matrix metalloproteinase-2 enhance progression of clear cell- and serous-type ovarian carcinomas

Abstract

Clear cell adenocarcinomas (CA), unlike serous adenocarcinomas (SA) of the ovary, are often at stage I, are resistant to platinum-based drugs and have a poor prognosis. The causes of these differences are unclear. In this study, the differences in progression between CA and SA were examined in terms of apoptosis-related and tumor invasion-related factors. The 16 cases of CA and the 16 cases of SA were reviewed. Excised tissues were classified into primary or metastatic loci, and the expressions of survivin, Bcl-2 and matrix metalloproteinase-2 (MMP-2) in each locus immunohistochemically assayed. Whether the expression of each protein was correlated to prognosis was investigated and additionally the invasion ability of cell strains established from CA and SA were examined using in vitro invasion assay. CA at stage I showed significantly higher survivin expression than SA (p<0.05). In CA, survivin tended to be expressed higher in primary locus than in metastatic locus (p=0.068), however, Bcl-2 was expressed relatively higher in the latter (p=0.087). SA did not have these tendencies. While MMP-2 was expressed significantly higher in SA than in CA (p<0.05), and more so in metastatic locus than in primary locus of SA (p<0.05). Invasion assay showed that the invasion of cells derived from SA was significantly inhibited by tissue inhibitors of metalloproteinase-2, an MMP inhibitor. The disease-free interval was significantly shorter when survivin expression was observed in the nucleus. These results suggest that the expression of apoptosis inhibiting factors and enhanced invasion ability affect progression of CA and SA, respectively.