Abstract
The interesting preponderance of Chinese with colorectal carcinoma (CRC) amongst the three major ethnic groups in Malaysia prompted a study to determine DNA mismatch repair (MMR) status in our CRC and attempt correlation with patient age, gender and ethnicity as well as location, grade, histological type and stage of tumour. Histologically re-confirmed CRC, diagnosed between 1st January 2005 and 31st December 2007 at the Department of Pathology, University of Malaya Medical Centre, were immunohistochemically stained with monoclonal antibodies to MMR proteins, MLH1, MSH2, MSH6 and PMS2 on the Ventana Benchmark XT autostainer. Of the 142 CRC cases entered into the study, there were 82 males and 60 females (M:F=1.4:1). Ethnically, 81 (57.0%) were Chinese, 32 (22.5%) Malays and 29 (20.4%) Indians. The patient ages ranged between 15-87 years (mean=62.4 years) with 21 cases <50-years and 121 ≥50-years of age. 14 (9.9%) CRC showed deficient MMR (dMMR). Concurrent loss of MLH1 and PMS2 occurred in 10, MSH2 and MSH6 in 2 with isolated loss of MSH6 in 1 and PMS2 in 1. dMMR was noted less frequently amongst the Chinese (6.2%) in comparison with their combined Malay and Indian counterparts (14.8%), and was associated with right sided and poorly differentiated tumours (p<0.05). 3 of the 5 (60.0%) dMMR CRC cases amongst the Chinese and 1 of 9 cases (11.1%) amongst the combined Malay and Indian group were <50-years of age. No significant association of dMMR was noted with patient age and gender, tumour stage or mucinous type.
Highlights
Colorectal carcinoma (CRC) is the most common malignancy in Malaysian males and third most common in females (Lim et al, 2008)
The tumour was classified as having deficient mismatch repair (MMR) when there was unequivocal loss of tumour nuclear staining (Figure 1) for one or more of the MMR proteins, MLH1, MSH2, MSH6 or PMS2, in the presence of immunoreactivity in the internal positive controls
Considering that MMR status of the CRCs in this study appears to be influenced by ethnicity, tumour location and grade, 3 of 5 cases (60.0%) of deficient MMR (dMMR) amongst the Chinese and 1 of 9 cases (11.1%) amongst the combined Malay and Indian group were
Summary
Colorectal carcinoma (CRC) is the most common malignancy in Malaysian males and third most common in females (Lim et al, 2008). Malaysia shows a unique racial distribution of its population with multiple ethnic groups, the three major being Malays, Chinese and Indians. Age-standardised incidence per 100,000 population for cases of CRC diagnosed in 2003-2005 demonstrated a preponderance of Chinese (31.5, 15.7 and 12.3 for Chinese, Indian and Malay males respectively and 26.2, 12.9, and 9.7 for Chinese, Indian, and Malay females). Whilst the Indians and Malays shared a seemingly close age-standardised incidence per 100,000 population, the Chinese had almost double the rate of CRC compared with the other two races. A similar trend of the age-standardised incidence rates between Chinese, Indians and Malays, is seen in neighbouring. Singapore with one minor variation viz Singaporean Malay males had a higher incidence rate compared with Singaporean Indian males but both remained below Singaporean Chinese males (Lim et al, 2008). Apart from attempting to determine whether MSI status, as represented by proficient or deficient MMR protein expression, differs between our major ethnic groups, we attempted to correlate MMR status with age and gender of patients and location, grade, histological type and stage of the CRC
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