title: Immunohistochemical survey of mismatch repair protein expression in uterine sarcomas and carcinosarcomas.
abstract: Uterine sarcomas and carcinosarcomas are an aggressive group of uterine malignancies. The frequency of mismatch repair (MMR) protein loss by immunohistochemical evaluation has not been comprehensively characterized in this group of tumors; hence, the appropriateness of applying an immunohistochemical panel to screen for Lynch syndrome in these tumors remains unclear. We examined for the immunohistochemical loss of 4 MMR proteins (MLH1, MSH2, MSH6, and PMS2) in a series of 67 uterine carcinosarcomas and 51 uterine sarcomas (20 leiomyosarcomas, 11 adenosarcomas, 9 low-grade endometrial stromal sarcomas, 8 high-grade endometrial stromal sarcomas/undifferentiated endometrial sarcomas, and 3 rhabdomyosarcomas) at our institution. Four of the 67 (6.0%) carcinosarcomas demonstrated abnormal MMR protein expression. Two tumors showed concurrent loss of MLH1 and PMS2 in both the carcinomatous and sarcomatous components. One tumor showed the loss of only PMS2 in both components. The remaining tumor showed an isolated loss of MLH1 and PMS2 in only the small cell carcinoma component, whereas the non-small-cell carcinoma and sarcoma components demonstrated normal staining patterns for MMR proteins. Two of 20 leiomyosarcomas (10%) showed the loss of MMR proteins: one with loss of PMS2 and the other with loss of MSH2 and MSH6. All other uterine sarcoma types examined showed intact MMR protein expression. These observations provide a basis for MMR protein screening in uterine carcinosarcomas and leiomyosarcomas but not in other types of uterine mesenchymal or mixed epithelial/mesenchymal malignancies.
authors.affiliation: Department of Pathology and Laboratory Medicine (L.N.H., S.L., C.B.G., C.-H.L.), University of British Columbia, Genetic Pathology Evaluation Centre, Vancouver, British Columbia, Canada Department of Laboratory Medicine and Pathology (C.-H.L.), Royal Alexandra Hospital and University of Alberta, Edmonton, Alberta, Canada Department of Pathology (R.H.A.), Faculty of Medicine, Health Sciences Center, Kuwait University, Kuwait.
authors.forename: Lien N
authors.initials: LN
authors.lastname: Hoang
authors.forename: Rola H
authors.initials: RH
authors.lastname: Ali
authors.forename: Sherman
authors.initials: S
authors.lastname: Lau
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002296:Carcinosarcoma / Q000378:metabolism* / Q000473:pathology; D045643:DNA Repair Enzymes / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D012509:Sarcoma / Q000378:metabolism* / Q000473:pathology; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes