Allelotype analysis of common epithelial ovarian cancers with special reference to comparison between clear cell adenocarcinoma with other histological types

Abstract

Determination of the histological type of epithelial ovarian cancer is clinically important to predict patient prognosis. To estimate accurately the chromosomal regions that frequently show loss of heterozygosity (LOH) in each histological type, LOH at 55 loci on 38 chromosomal arms was examined by means of laser capture microdissection and PCR-LOH analysis in 45 epithelial ovarian cancers composed of clear cell adenocarcinoma (CCA), serous adenocarcinoma (SEA), endometrioid adenocarcinoma (EMA) and mucinous adenocarcinoma (MUA). In addition, p53 (exons 5 - 8) gene mutations and the nuclear immunoreactivity of p53 proteins in these tumors were examined by PCR-SSCP and immunohistochemistry. In CCA, LOH was detected primarily on 1p (69%) followed by 19p (45%) and 11q (43%). On the other hand, in SEA, LOH was detected in at least 50% of cases on 1p, 4p, 5q, 6p, 8p, 9q, 12q, 13q, 15q, 16p, 17p, 17q, 18p, 18q, 19p, 20p and Xp. The incidences of LOH on 5q, 12q, 13q and 17p were significantly lower in CCA than in SEA (P = 0.019, 0.031, 0.0035 and 0.012). EMA showed a tendency for frequent LOH on 7p, whereas MUA showed significantly high occurrence of LOH at 17p13.1. The incidences of p53 mutation and p53 nuclear immunoreactivity also differed between CCA and SEA: 0% and 7% in the former and 64% and 45% in the latter (P = 0.0006 and 0.039). These findings clarify that there are differences in LOH distribution patterns among different histological subtypes of epithelial ovarian cancer. In CCA, p53 tumor-suppressor gene (TSG) is not involved in carcinogenesis and tumor-suppressor genes located on 1p are considered to play an important role in tumor development.