Abstract
Right and left-sided colorectal carcinoma (CRC) are generally observed to differ in pathogenetic mechanisms, with deficiency of DNA mismatch repair (dMMR) leading to microsatellite instability occurring more commonly on the right. A study to assess the DNA mismatch repair status and presence of CD133-putative stem cells in 40 consecutive right and 40 left-sided formalin-fixed, paraffin-embedded CRC was carried out at the Department of Pathology, University of Malaya Medical Centre. Immunohistochemical staining for DNA mismatch repair gene products, MLH1, MSH2, MSH6 and PMS2 and CD133 were carried out on a Ventana XT autostainer. dMMR was significantly increased in right-sided (35%) compared with left-sided (0%) CRC. Of the dMMR cases, 10 had concomitant loss of MLH1 and PMS2, two concomitant loss of MSH2 and MSH6, one isolated loss of MSH6 and another of PMS2. CD133 immunoexpression score, arbitrarily computed as the semi-quantitative estimation of proportion of CRC immunopositive cells multiplied by intensity of staining was significantly lower (<i>p</i><0.05) in right (mean score=7.0) compared with left-sided tumours (mean score=9.9). The observations of a higher frequency of dMMR and lower CD133 expression in right-sided CRC further support the notion of dissimilar mechanisms involved in aetiology and evolution of right and left-sided tumours.
Published Version
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