title: Immunohistochemical expression pattern of MMR protein can specifically identify patients with colorectal cancer microsatellite instability.
abstract: The microsatellite instability (MSI) pathway is found in most cases of hereditary nonpolyposis colorectal cancer (HNPCC) and in 12 % of sporadic colorectal cancer (CRC). It involves inactivation of deoxyribonucleic acid mismatch repair (MMR) genes MLH1, MSH2, PMS2, and MSH6. MMR germline mutation detections are an important supplement to HNPCC clinical diagnosis. It enables at-risk and mutation-positive relatives to be informed about their cancer risks and to benefit from intensive surveillance programs that have been proven to reduce the incidence of CRC. In this study, we analyzed for the first time in Tunisia the potential value of immunohistochemical assessment of MMR protein to identify microsatellite instability in CRC. We evaluate by immunohistochemistry MMR protein expression loss in tumoral tissue compared to positive expression in normal mucosa. Immunohistochemistry revealed loss of expression for MLH1, MSH2, MSH6, and PMS2 in 15, 21, 13, and 15 % of cases, respectively. Here, we report a more elevated frequency of MSI compared to data of the literature. In fact, by immunohistochemistry, 70 % of cases were shown to be MSS phenotype, whereas 30 % of cases, in our set, were instable. Moreover, according to molecular investigation, 71 % of cases were instable (MSI-H) and remaining cases were stable (29 %). Thus, we found a perfect association between MMR immunohistochemical analyses and MSI molecular investigation. Immunohistochemical analysis of MMR gene product expression may allow one to specifically identify MSI phenotype of patients with colorectal carcinomas.
authors.affiliation: Department of Pathology, Charles Nicolle Hospital, Tunis, Tunisia, arfaouiamira@hotmail.com.
authors.forename: Arfaoui Toumi
authors.initials: AT
authors.lastname: Amira
authors.forename: Trabelsi
authors.initials: T
authors.lastname: Mouna
authors.forename: Blel
authors.initials: B
authors.lastname: Ahlem
authors.forename: Aloui
authors.initials: A
authors.lastname: Raoudha
authors.forename: Ben Hmida
authors.initials: BH
authors.lastname: Majid
authors.forename: Hamza
authors.initials: H
authors.lastname: Amel
authors.forename: Zermani
authors.initials: Z
authors.lastname: Rachida
authors.forename: Kourdaa
authors.initials: K
authors.lastname: Nadia
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000251:Adenosine Triphosphatases / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D053843:DNA Mismatch Repair / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D014416:Tunisia
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