title: Expression of hMLH1, hMSH2 and hMSH6 in small intestinal carcinomas.
abstract: OBJECTIVE
  Although primary small intestinal carcinoma (SIC) is morphologically similar to colorectal carcinoma and shares many of the genetic changes of carcinogenesis, little is known about the role of defective mismatch repair (MMR) genes involved in the SIC. The aim of this study is to investigate the role of defective MMR genes and correlation between clinicopathological factors and loss of MMR protein in SIC.
  
  
  METHODS
  A total of 195 SIC cases were collected from 20 institutions in Korea and tissue microarrays (TMA) were made. The loss of expression of hMLH1, hMSH2 and hMSH6 was examined by immunohistochemistry (IHC).
  
  
  RESULTS
  The loss of expression of hMLH1, hMSH2 and hMSH6 was identified in 25/193 (13.0%), 25/193 (13%) and 29/195 (15%), respectively. The loss of hMSH2 expression was associated with retroperitoneal seeding. Patients with loss of hMSH6 expression had a tendency to invade deeply and a higher frequency of pancreas invasion. The loss of hMSH6 expression was associated less frequently with peritumoral adenoma. There was no survival difference by MMR protein expression status.
  
  
  CONCLUSIONS
  The loss of MMR protein was associated with some distinct clinicopathological features. MMR pathway seems to be major pathway in carcinogenesis of SICs. MMR defect seems to be related with sporadic-microsatellite instability (MSI).
authors.affiliation: Department of Pathology, Yeungnam University College of Medicine, Daegu, Korea.
authors.forename: Mi Jin
authors.initials: MJ
authors.lastname: Gu
authors.forename: Young Kyung
authors.initials: YK
authors.lastname: Bae
authors.forename: Aeri
authors.initials: A
authors.lastname: Kim
authors.forename: Seung-Mo
authors.initials: SM
authors.lastname: Hong
authors.forename: Eunsil
authors.initials: E
authors.lastname: Yu
authors.forename: Jihun
authors.initials: J
authors.lastname: Kim
authors.forename: Kee-Taek
authors.initials: KT
authors.lastname: Jang
authors.forename: Hee-Kyung
authors.initials: HK
authors.lastname: Chang
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Jung
authors.forename: Han-Ik
authors.initials: HI
authors.lastname: Bae
authors.forename: Ghil Suk
authors.initials: GS
authors.lastname: Yoon
authors.forename: Joon Mee
authors.initials: JM
authors.lastname: Kim
authors.forename: Jung Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Gwang Il
authors.initials: GI
authors.lastname: Kim
authors.forename: Young-Ha
authors.initials: YH
authors.lastname: Oh
authors.forename: Kyu Yun
authors.initials: KY
authors.lastname: Jang
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Jun
authors.forename: Dae Woon
authors.initials: DW
authors.lastname: Eom
authors.forename: Kye Won
authors.initials: KW
authors.lastname: Kwon
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
authors.forename: Jae Bok
authors.initials: JB
authors.lastname: Park
authors.forename: Soon Won
authors.initials: SW
authors.lastname: Hong
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Jung
authors.forename: Ji Shin
authors.initials: JS
authors.lastname: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D016009:Chi-Square Distribution; D053843:DNA Mismatch Repair; D004268:DNA-Binding Proteins / Q000032:analysis*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D007421:Intestine, Small / Q000737:chemistry* / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000032:analysis*; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000032:analysis*; D010179:Pancreas / Q000473:pathology; D011379:Prognosis; D056910:Republic of Korea; D012186:Retroperitoneal Neoplasms / Q000556:secondary; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; 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