CD44 expression in benign, premalignant, and malignant ovarian neoplasms: Relation to tumour development and progression

To clarify the possible role of CD44 expression in ovarian tumour developme nt and progression, an immunohistochemical investigation was undertaken of a series of 115 carcinomas, 32 tumors with low malignant potential (LMP), a nd 53 cystadenomas. A combination of the reverse transcription-polymerase c hain reaction (RT-PCR) and Southern blot hybridization (SBH) assays was als o performed for 17 malignant, four LMP, six cystadenoma, and seven normal o varian samples. Immunoreactivity scores for CD44s, CD44v3, and CD44v6 were significantly higher in LMP and malignant tumours than in the benign or nor mal cases, in line,vith the results of gross mRNA-based assays. Exon-specif ic RT-PCR/SBH assays revealed that the expression of large CD44 transcripts containing v6 to v8 exons and small isoforms containing v2 and v3 was comm on among normal and neoplastic tissues, while a simultaneous increase of la rge isoforms containing v2 to v5 was also revealed in LMP and malignant tum ours. In ovarian carcinomas, the scores for CD44s, CD44v3, and CD44v6 were inversely related to the FIGO stage, but there was no association with lymp h node status or expression of hormone receptors. Multivariate analysis rev ealed loss of CD44v3 expression to be an independent factor for poor surviv al. The findings indicate that CD44 is up-regulated during the development of ovarian carcinomas but is subsequently down-regulated daring their progr ession, resulting in aggressive behaviour and an unfavourable prognosis. Co pyright (C) 1999 John Wiley & Sons, Ltd.