Frequent down-regulation and lack of mutation of the KAI1 metastasis suppressor gene in epithelial ovarian carcinoma

Objective. KAI1 is a recently identified metastasis suppressor gene on huma n chromosome 11p11.2. It belongs to a structurally distinct family of cell surface glycoproteins. Decreased KAI1 expression seems to be involved in th e progression of human prostate, lung, pancreatic, and possibly breast canc er, and recently a reduced KAI1 protein expression has been demonstrated in several ovarian carcinoma cell lines. The aim of this study is to determin e whether the KAI1 gene is altered in human epithelial ovarian carcinomas. In addition, its prognostic significance in this tumor is also evaluated. Methods. To detect KAI1 expression, 102 tumor samples from benign, borderli ne, primary invasive, metastatic, and recurrent epithelial ovarian tumors w ere prepared for immunohistochemical study with C-16, an anti-KAI1 polyclon al antibody. In addition, cellular RNA from 24 primary invasive and 7 recur rent tumors was also analyzed for KAI1 expression by using a reverse transc riptase PCR (RT-PCR) technique. The PCR single-strand conformation polymorp hism method and direct DNA sequencing were used to detect KAI1 mutation in the 44 primary invasive and 8 recurrent ovarian carcinomas. Results. In immunohistochemical study, decrease of KAI1 protein expression was associated with the progression of ovarian tumor. However, it had no re lation to the stage of primary invasive cancers because of its frequent occ urrence in early stage tumors. KAI1 expression was also frequently down-reg ulated in primary invasive and recurrent tumors in RT-PCR analysis. Except for a missense change at codon 241 (ATC to GTC), which causes the substitut ion of a valine for an isoleucine in the amino acid sequence and occurs in both normal and tumor tissues, no mutation of the KAI1 gene was found in an y of the 52 carcinomas. Although there was a trend for deteriorating surviv al from patients with KAI1-preserved tumors to those with KAI1-decreased an d -negative tumors, statistically it was not significant (P = 0.079). Conclusion. KAI1 may play a role in the malignant progression of epithelial ovarian carcinoma through the down-regulation of expression rather than ge ne mutation. Since the decreased expression presented frequently in early s tage tumors, it may be an early event in the progression of this tumor and its prognostic significance needs further investigation with a larger numbe r of cases. (C) 2000 Academic Press.