Immunohistochemical analysis of mismatch repair proteins in colorectal adenomas

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Rammeh Soumaya
Sabbegh Znaidi Nadia
Arfaoui Amira
Ayouni Kaouther
Blel Ahlem
Farah Faten
Zidi Yosra
Najjar Taoufik
Kourda Nadia
Said Yosra
Zermani Rachida

Abstract

Background: The deficiency of mismatch repair system is one of the main pathways in colorectal cancer. This system consists mainly of four proteins: MLH1, MSH2, MSH6 and PMS2. Colorectal cancer develops in the majority of cases from precancerous lesions called adenomas. Only few studies have reported on the deficiencies of these proteins in adenomas.

Aim: In this study we used immunohistochemistry staining in colorectal adenomas to assay functional status of MLH1, MSH2, MSH6, and PMS2 proteins. Methods: 102 adenomas from 93 patients were collected in our institution during six years (2007-2012). The immunohistochemical technique was performed with 4 antibodies: MLH1, MSH2, MSH6 and PMS2. The loss of expression was retained if adenomatous cells were not stained with positive internal control. Staining was considered as abnormal if nucleus of adenomatous cells showed low nuclear staining and / or heterogeneous one, while positive internal control had normal staining.

Results: Loss of expression of MSH2 and MSH6 in adenomatous cells was found in only 1 case which was a tubular adenoma 3mm high-grade dysplasia. Abnormal staining of the adenomatous cells was noted in 23 cases (22.5%) for MSH2 and in 8 cases (7.8%) for MSH6. No cases showed loss of expression of MLH1 and PMS2. Abnormal expression of MSH2 and MSH6 was not correlated with sex of patients, the location of the adenoma, its grade of dysplasia and its histological type.

Conclusions: Loss of Mismatch repair proteins expression is a rare event in adenomas. However, the abnormal expression levels are higher in our study compared to those reported in the literature. This could reflect a higher rate of microsatellite instability in our patients. Multicenter and larger studies with molecular biology techniques are needed.

Keywords:

Colorectal cancer, Adenoma, Immunohistochemistry, Mismatch Repair Proteins

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References

  1. Piard F, Martin L, Chapusot C et al. Les voies de la carcinogenèse colorectale : intérêt et application pour le pathologiste. Ann Pathol 2002;22 : 277-88.
  2. Paraf F. Comment et quand rechercher une instabilité des microsatellites dans les cancers colorectaux en 2008? Ann Pathol 2007;27:433-8.
  3. Lindor NM, Burgart LJ, Leontovich Oet al. Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol 2002, 20:1043-8
  4. Iyer R, Pluciennik A, Burdett V, Modrich P. DNA mismatch repair: Functions and mechanisms. Chem Rev 2006;106:302-23.
  5. Lynch HT,Lynch JF: Hereditary nonpolyposis colorectal cancer. Seminars in Surgical Oncology 18: 305-313, 2000.
  6. Marcus V, Madlensky L, Gryfe R. Immunohistochemistry for hMLH1 and hMSH2: A practical test for DNA mismatch repair-deficient tumors. Am J Surg Pathol 1999;23:1248-55.
  7. Chaves P, Cruz C, Lage P. Immunohistochemical detection of mismatch repair gene proteins as a useful tool for the identification of colorectal carcinoma with the mutator phenotype. J Pathol 2000;191:355-60
  8. Walsh MD, Buchanan DD, Pearson SAet al. Immunohistochemical testing of conventional adenomas for loss of expression of mismatch repair proteins in Lynch syndrome mutation carriers: a case series from the Australasian site of the colon cancer family registry. Mod Pathol. 2012;25722-30.
  9. Pino MS, Mino-Kenudson M, Wildemore BMet al. Deficient DNA mismatch repair is common in Lynch syndrome-associated colorectal adenomas. J Mol Diagn. 2009;11:238-47.
  10. Molaei M, Yadollahzadeh M, Almasi S et al. Sporadic colorectal polyps and mismatch repair proteins. Indian J Pathol Microbiol. 2011;54:725-9
  11. Balbinotti RA, Ribeiro U JR, Sakai P, et al. hMLH1, hMSH2 and cyclooxygenase-2 (cox-2) in sporadic colorectal polyps. Anticancer Res. 2007;27:4465-71
  12. Petko Z, Ghiassi M, Shuber Aet al. Aberrantly methylated CDKN2A, MGMT, and MLH1 in colon polyps and in fecal DNA from patients with colorectal polyps. Clin Cancer Res 2005;11:1203-9
  13. Puissieux A. Analyse génotypique et immunohistochimique dans les cancers humains: confrontation ou complementary? Ann Pathol. 2002 ; 22 :93-5.
  14. Grassi J, Verney C, Walker F,et al. Les contrôles nécessaires en immunohistochimie : de la recherche au diagnostic. Ann Pahol 2007;27 :16-26
  15. Taniere P, Joly MO. Pathologie moléculaire du cancer du côlon : vers la mise en place de stratégies diagnostiques intégrées. Ann Pathol 2002 ; 22 : 253-341.