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Updated: Apr 15, 2026
Deficient Pms2, ERCC1, Ku86, CcOI in Field Defects During Progression to Colon Cancer
Published on: July 28, 2010
[Immunohistochemical analysis of mismatch repair proteins in colorectal adenomas]
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.
Insights
Mismatch repair protein deficiency is rare in colorectal adenomas, but abnormal expression was more frequent in this study. Further research is needed to understand its implications for microsatellite instability.
Area of Science:
- Oncology
- Gastroenterology
- Molecular Biology
Context:
- Mismatch repair (MMR) deficiency is a key pathway in colorectal cancer development.
- Colorectal cancers often arise from adenomas, which are precancerous lesions.
- Few studies have investigated MMR protein status in adenomas.
Purpose:
- To assess the functional status of MLH1, MSH2, MSH6, and PMS2 proteins in colorectal adenomas using immunohistochemistry.
- To determine the prevalence of MMR protein deficiency and abnormal expression in adenomas.
Summary:
- Immunohistochemistry was performed on 102 colorectal adenomas from 93 patients.
- Loss of MSH2 and MSH6 expression was observed in only one case.
- Abnormal MSH2 and MSH6 expression was noted in 22.5% and 7.8% of cases, respectively.
- No loss of MLH1 or PMS2 expression was detected.
Impact:
- Abnormal MMR protein expression in adenomas, though rare, was higher than previously reported.
- Findings suggest a potential for increased microsatellite instability in the patient cohort.
- Highlights the need for larger, multicenter studies incorporating molecular techniques to further elucidate MMR protein roles in adenoma development.
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