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Published on: July 28, 2010
The expression of Mutl Protein Homolog 1 (MLH1) and Muts Homolog 2 (MSH2) in colorectal carcinoma: An
Eshita Garg1, Manisha Sharma1, Manas Madan1
1Department of Pathology, S.G.R.D Medical College, Sri Amritsar, Punjab, India.
Background:
The development of colorectal carcinoma is a complicated multistep process that involves the accumulation of mutations in tumor suppressor genes and oncogenes. Lynch syndrome or hereditary non-polyposis colorectal carcinoma is a cancer syndrome that accounts for around 11% of cases of colorectal carcinoma and is caused by germline mutation in one or more of mismatch repair genes, that is MutL Homolog 1 and MutS Homolog 2 .
Aim:
To study the immunohistochemistry of MLH1 and MSH2 mis match repair (MMR) proteins in colorectal carcinoma (CRC) and to study the association of abnormal MMR protein expression with clinicopathological parameters.
Materials And Methods:
This study included 41 cases of colectomy specimens submitted to the pathology department of Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar. Immunohistochemistry stains using antibodies MLH1 and MSH2 were performed on representative tissue blocks. The results were interpreted and correlated with other parameters like age, gender, site, size, histological grading, staging, lymph node status, and lymphovascular invasion.
Results:
A total of 41 cases of CRC were studied, which included 24 females and 17 males. Twenty-four cases (58.5%) were > 50 years of age, and the most commonly involved site of tumor was the ascending colon, accounting for 21 cases (51.2%). Sixteen out of 41 cases (39%) showed loss of immunohistochemistry (IHC) staining for MLH1 and MSH2. Out of 16 MMR-deficient cases, 11 cases show concurrent loss of MLH1 and MSH2. Isolated loss of MLH1 is seen in five cases. No isolated loss of MSH2 seen. The tumors with Mis match Repair - deficient status showed a significant correlation with grade of tumor, stage of tumor, lymphovascular invasion and lymph node status. However, no significant correlation was found between MMR status and age, gender of the patient, and size of the tumor.
Conclusion:
IHC test for detection of MLH1 and MSH2 expression represents a rapid, reliable, and cost-effective method to detect MMR deficiency in CRC tumors. Expression of MMR protein demonstrated significant association with grade of tumor, stage of tumor, lymphovascular invasion, and lymph node status.
