Microsatellite instability and expression of hMLH1 and hMSH2 proteins in ovarian endometrioid cancer.
Microsatellite instability and loss of heterozygosity has been implicated in ovarian carcinogenesis. The reported frequency of microsatellite instability in human ovarian cancer varies significantly owing to the use of heterogeneous tumor histotypes and various microsatellite markers in different laboratories. In this study, we determined the frequency of microsatellite instability in 74 ovarian endometrioid carcinomas using four microsatellite markers (BAT25, BAT26, D5S346, D17S250), and examined hMLH1 and hMSH2 protein expression. In all, 20% of the tumors were microsatellite instability high (two or more markers showing instability) and 12% were microsatellite instability low (one marker showed instability). Loss of hMLH1 and/or hMSH2 expression was found in nine of 15 microsatellite instability-high tumors. The microsatellite instability-high phenotype tended to occur more frequently in low-grade tumors (P=0.053), but did not correlate with clinical stage. Totally, 38% of cases also displayed loss of heterozygosity at D17S250; this loss of heterozygosity was associated with high clinical stage (P=0.097). Our results indicate that both microsatellite and loss of heterozygosity at D17S250 are involved in the development of ovarian endometrioid carcinoma.
Liu
Jinsong
J
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. jliu@mdanderson.org
Albarracin
Constance T
CT
Chang
Ki-Hong
KH
Thompson-Lanza
Jennifer A
JA
Zheng
Wenxin
W
Gershenson
David M
DM
Broaddus
Russell
R
Luthra
Rajyalakshmi
R
D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis*; D018269:Carcinoma, Endometrioid / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity; D053842:Microsatellite Instability; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000032:analysis*; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis*; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology; D010641:Phenotype
D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein