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

  • Juhari, Wan Khairunnisa Wan (Department of Paediatric, Universiti Sains Malaysia, Health Campus) ;
  • Rahman, Wan Faiziah Wan Abdul (Department of Pathology, Universiti Sains Malaysia, Health Campus) ;
  • Sidek, Ahmad Shanwani Mohd (Surgery Department, Hospital Raja Perempuan Zainab 2) ;
  • Hassan, Muhammad Radzi Abu (Clinical Research Centre, Hospital Sultanah Bahiyah) ;
  • Noordin, Khairul Bariah Ahmad Amin (School of Dental Sciences, Universiti Sains Malaysia) ;
  • Zakaria, Andee Dzulkarnaen (Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia, Health Campus) ;
  • Macrae, Finlay (Department of Colorectal Medicine and Genetics, Royal Melbourne Hospital) ;
  • Zilfalil, Bin Alwi (Department of Paediatric, Universiti Sains Malaysia, Health Campus)
  • Published : 2015.05.18

Abstract

Background: Lynch syndrome (LS) is an inherited predisposition to colorectal, endometrial (uterine) and other cancers. Although most cancers are not inherited, about 5 percent (%) of people who have colorectal or endometrial 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 Malay cohort by immunohistochemistry. Materials and Methods: A total of 17 patients were selected fulfilling one of the Bethesda criteria: colorectal cancer diagnosed in a patient aged less than 50 years old, having synchronous and metachronous colorectal cancer or with a strong family history. Immunohistochemical staining was performed on 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 had abnormal immunohistochemical staining with one or more of the four antibodies. Loss of expression were noted in 13 tumour tissues with a negative staining score <4. Of 13 tumour tissues, four showed loss expression of MLH1. For PMS2, loss of expression were noted in five cases. Both MSH2 and MSH6 showed loss of expression in two tumour tissues respectively. Conclusions: Revised Bethesda criteria and immunohistochemical analysis constituted a convenient approach and is recommended to be a first-line screening for Lynch syndrome in Malay cohorts.

Keywords

Colorectal carcinoma;HNPCC;Lynch syndrome;immunohistochemistry;MMR

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