title: Microsatellite instability and alteration of the expression of hMLH1 and hMSH2 in ovarian clear cell carcinoma.
abstract: Microsatellite instability (MSI) is commonly seen in tumors associated with the hereditary nonpolyposis colorectal cancer syndrome and is caused by defects in the DNA mismatch repair genes. MSI has also been observed in various sporadic cancers, including colorectal, gastric, and endometrial. The role and incidence of MSI in ovarian clear cell carcinoma remain unknown. This study was conducted to evaluate the frequency of MSI in ovarian clear cell carcinomas and to evaluate the sensitivity and specificity of immunohistochemistry in predicting mismatch-repair gene deficiency. A total of 42 ovarian clear cell carcinomas were analyzed for MSI using a panel of 5 microsatellite markers (BAT25, BAT26, D5S346, D2S123, and D17S250). Alterations in the expression of hMLH1 and hMSH2 proteins in these tumors were examined. Of the 42 ovarian clear cell tumors analyzed, 6 demonstrated a high level of MSI (MSI-H), 3 demonstrated a low level of MSI (MSI-L), and the remaining 33 exhibited microsatellite stability (MSS). No correlation was found between MSI level and patient age or tumor stage or size (P >0.05). Loss of expression of either hMLH1 or hMSH2 was observed in 4 of the 6 (67.7%) MSI-H tumors, whereas 34 of the 36 (94.4%) MSI-L or MSS tumors expressed both the hMLH1 and hMSH2 gene products. Our results indicate that MSI-H is involved in the development of a subset of ovarian clear cell carcinomas. A strong correlation exists between alterations in the expression of hMLH1 and hMSH2 and the presence of MSI-H in these tumors. However, immunohistochemical testing alone may miss a small fraction of cases with MSI-H.
authors.affiliation: Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Kathy Qi
authors.initials: KQ
authors.lastname: Cai
authors.forename: Constance
authors.initials: C
authors.lastname: Albarracin
authors.forename: Daniel
authors.initials: D
authors.lastname: Rosen
authors.forename: Rocksheng
authors.initials: R
authors.lastname: Zhong
authors.forename: Wenxin
authors.initials: W
authors.lastname: Zheng
authors.forename: Rajyalakshmi
authors.initials: R
authors.lastname: Luthra
authors.forename: Russell
authors.initials: R
authors.lastname: Broaddus
authors.forename: Jinsong
authors.initials: J
authors.lastname: Liu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D018262:Adenocarcinoma, Clear Cell / Q000235:genetics*; D000328:Adult; D000368:Aged; D002352:Carrier Proteins; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D010051:Ovarian Neoplasms / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein