Tumor Biology

, Volume 35, Issue 7, pp 6283–6291 | Cite as

Immunohistochemical expression pattern of MMR protein can specifically identify patients with colorectal cancer microsatellite instability

  • Arfaoui Toumi Amira
  • Trabelsi Mouna
  • Blel Ahlem
  • Aloui Raoudha
  • Ben Hmida Majid
  • Hamza Amel
  • Zermani Rachida
  • Kourdaa Nadia
Research Article


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.


Colorectal carcinomas Immunohistochemistry MSI phenotype MSI status MMR genes Microsatellite instability 



This study was supported by a grant from the Ministry of Higher Education and Scientific Research of Tunisia. We thank Dr. Marie Pierre Buisine who performed all the molecular analyses in the Laboratory of Biochemistry and Molecular Biology HMNO, Department of Oncology and Molecular Genetics, University Hospital of Lille, 59000 Lille, France.

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Arfaoui Toumi Amira
    • 1
    • 3
  • Trabelsi Mouna
    • 1
  • Blel Ahlem
    • 1
  • Aloui Raoudha
    • 1
  • Ben Hmida Majid
    • 2
  • Hamza Amel
    • 1
  • Zermani Rachida
    • 1
  • Kourdaa Nadia
    • 1
  1. 1.Department of PathologyCharles Nicolle HospitalTunisTunisia
  2. 2.Department of Preventive MedicineMedical University of TunisiaTunisTunisia
  3. SoukraTunisia

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