title: Clinicopathologic analysis with immunohistochemistry for DNA mismatch repair protein expression in synchronous primary endometrial and ovarian cancers.
abstract: OBJECTIVE
  Synchronous primary endometrial and ovarian cancers have been an important topic in clinical medicine because it is sometimes difficult to distinguish whether there are 2 primary tumors or a single primary tumor and an associated metastasis. In addition, although these tumors are recommended for either immunohistochemistry for DNA mismatch repair (MMR) proteins or a microsatellite instability test in the Bethesda guidelines as Lynch syndrome-associated cancers, few studies have completed these analyses. In this study, we characterized the clinicopathologic features and the expression pattern of MMR proteins in synchronous primary endometrial and ovarian cancers.
  
  
  METHODS
  Clinicopathologic features and the expression pattern of MMR proteins (MLH1, MSH2, and MSH6) were characterized and analyzed in 32 synchronous primary endometrial and ovarian cancers.
  
  
  RESULTS
  Most synchronous cancers are endometrioid type (endometrioid/endometrioid) (n = 24, 75%), grade 1 (n = 19, 59.4%), and diagnosed as stage I (n = 15, 46.9%) in both endometrium and ovary. It is worth mentioning that 75% of the patients (n = 24) had endometriosis, which was more common (n = 21, 87.5%) in endometrioid/endometrioid cancers, whereas only 3 cases (37.5%) were of different histology (P = 0.018). Loss of expression of at least 1 MMR protein was observed in 17 (53.1%) of the endometrial tumors and in 10 (31.3%) of ovarian tumors. Only 4 cases (12.5%) that had specific MMR protein loss showed the same type of loss for both endometrial and ovarian tumors, in which 3 of the cases were losses in MLH1. One case showed concordant MSH6 protein loss, although the cases did not meet the Amsterdam criteria II.
  
  
  CONCLUSIONS
  These results suggest that most synchronous primary endometrial ovarian cancers are not hereditary cancers caused by germ line mutations but rather sporadic cancers.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Kanako
authors.initials: K
authors.lastname: Nakamura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nomura
authors.forename: Kouji
authors.initials: K
authors.lastname: Banno
authors.forename: Haruko
authors.initials: H
authors.lastname: Irie
authors.forename: Masataka
authors.initials: M
authors.lastname: Adachi
authors.forename: Miho
authors.initials: M
authors.lastname: Iida
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Umene
authors.forename: Yuya
authors.initials: Y
authors.lastname: Nogami
authors.forename: Kenta
authors.initials: K
authors.lastname: Masuda
authors.forename: Iori
authors.initials: I
authors.lastname: Kisu
authors.forename: Arisa
authors.initials: A
authors.lastname: Ueki
authors.forename: Wataru
authors.initials: W
authors.lastname: Yamagami
authors.forename: Fumio
authors.initials: F
authors.lastname: Kataoka
authors.forename: Akira
authors.initials: A
authors.lastname: Hirasawa
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Tominaga
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Susumu
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis; D000230:Adenocarcinoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D002296:Carcinosarcoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D053843:DNA Mismatch Repair; D004268:DNA-Binding Proteins / Q000032:analysis; D016889:Endometrial Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000032:analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009378:Neoplasms, Multiple Primary / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D009687:Nuclear Proteins / Q000032:analysis; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000235:genetics / 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; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein