Comparison of serous and mucinous ovarian carcinomas: Distinct pattern of allelic loss at distal 8p and expression of transcription factor GATA-4

Using comparative genomic hybridization (CGH), we have previously demonstra ted frequent loss of 8p, especially its distal part, in ovarian carcinoma. To compare the deletion map of distal 8p in serous and mucinous ovarian car cinomas, we performed allelic analysis with 18 polymorphic microsatellite m arkers at 8p21-p23. In serous carcinoma. loss of heterozygosity (LOH) was d etected in 67% of the samples, and the majority of the carcinomas showed lo ss of all or most of the informative markers. in contrast, only 21% of muci nous carcinomas showed allelic loss, with only one or two loci showing LOH in each sample. in serous carcinomas, LOH was associated with higher grade tumors. Three distinct minimal common regions of loss could be defined in s erous carcinomas (at 8p21.1, 8p22-p23.1, and 8p23.1). Expression of a trans cription factor gene, GATA4, located at one of these regions (8p23.1) was s tudied in serous and mucinous ovarian carcinomas by Northern blotting and i mmunohistochemical staining of tumor microarray. Expression was found to be lost in most serous carcinomas but retained in the majority of mucinous ca rcinomas. Our results suggest distinct pathogenetic pathways in serous and mucinous ovarian carcinomas and the presence of more than one tumor suppres sor gene at 8p involved in the tumorigenesis of serous carcinoma.