A novel germline mutation of MSH2 in a hereditary nonpolyposis colorectal cancer patient with liposarcoma

BACKGROUND: One of the clinical features of hereditary nonpolyposis colorectal cancer (HNPCC) is a high incidence of multiple primary neoplasms arising in various organs including the gastrointestinal and genitourinary tracts. Among extracolonic tumors, a limited number of soft tissue sarcomas associated with HNPCC have been reported, and the mechanism underlying liposarcoma in HNPCC patients remains unclear. AIM: We herein report the case of a HNPCC patient with liposarcoma, with the goal of elucidating the involvement of a mismatch repair deficiency in the tumor. METHODS AND RESULTS: A 40-yr-old Japanese patient, who had a past history of adenocarcinoma of the rectum and transitional cell carcinoma of the urinary bladder, developed a liposarcoma in his left thigh. Although his family history did not fulfill the revised Amsterdam criteria, his blood sample was subjected to genetic testing. Direct sequencing of the genomic DNA from the blood identified an AT deletion at codon 677 in exon 13 of hMSH2, a pathogenic mutation that has not been reported before. The expression of MSH2 in the liposarcoma and rectal cancer of the patient was analyzed by immunohistochemistry, which revealed loss of MSH2 expression in the tumors. To investigate whether the loss of MSH2 was a common feature of liposarcoma, we examined the MSH2 expression in an additional two sporadic liposarcomas, both of which were stained with anti-MSH2 antibody. CONCLUSION: We identified a novel pathogenic germline mutation of MSH2 in an HNPCC patient. Since an immunohistochemical analysis showed no nuclear staining for MSH2 protein in the liposarcoma as well as the rectal cancer, the loss of wild-type MSH2 protein was thus considered to possibly play a role in the development of liposarcoma in HNPCC patients.