Analysis of Hereditary Nonpolyposis Colorectal Cancer in Malay Cohorts using Immunohistochemical Screening

Background: Lynch syndrome (LS) is an inherited predisposition to colorectal, endometrial (uterine) andother cancers. Although most cancers are not inherited, about 5 percent (%) of people who have colorectal orendometrial cancer have the Lynch syndrome. It involves the alteration of mismatch repair (MMR) genes; MLH1,MSH2, MSH6 or PMS2. In this study, we analyzed the expression of MMR proteins in colorectal cancer in a Malaycohort by immunohistochemistry. Materials and
Methods: A total of 17 patients were selected fulfilling one of theBethesda criteria: colorectal cancer diagnosed in a patient aged less than 50 years old, having synchronous andmetachronous colorectal cancer or with a strong family history. Immunohistochemical staining was performedon paraffin embedded tumour tissue samples using four antibodies: MLH1, MSH2, MSH6 and PMS2.
Results:Twelve out of 17 patients (70.6%) were noted to have a family history. A total of 41% (n=7) of the patients hadabnormal immunohistochemical staining with one or more of the four antibodies. Loss of expression were notedin 13 tumour tissues with a negative staining score <4. Of 13 tumour tissues, four showed loss expression ofMLH1. For PMS2, loss of expression were noted in five cases. Both MSH2 and MSH6 showed loss of expressionin two tumour tissues respectively.
Conclusions: Revised Bethesda criteria and immunohistochemical analysisconstituted a convenient approach and is recommended to be a first-line screening for Lynch syndrome in Malaycohorts.