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Prognostic Significance of HER2 and MLH1 Protein Expression in Colorectal Cancer

In colorectal cancer (CRC), numerous studies showed HER2 overexpression and amplification as a therapeutic and prognostic target. Further, it was suggested that genetic instability of mismatch repair gene MLH1 might increase negative predictive value of HER2 overexpression. Genetic or epigenetic inactivation of MLH1 gene is generally associated with loss of immunohistochemical expression of the corresponding protein. Hence, present study aimed to investigate the prevalence of HER2 and MLH1 protein expression by immunohistochemistry in untreated CRC patients (N=82) and further to examine their association with various clinicopathological variables and prognosis. Cytoplasmic HER2 and MLH1 protein expression was found in 31% and 29% of patients, respectively. With regard to clinicopathological parameters, incidence of MLH1 positivity was significantly higher in patients with adenocarcinomas as compared to mucinous adenocarcinomas (p=0.021). In relation to survival analysis, HER2 negative expression was associated with unfavorable RFS (p=0.074) and OS (p=0.027) as compared to HER2 positive expression in total patients. Further a trend of reduced OS was observed with HER2 negative expression in subgroups of patients with early stage (p=0.082), colon cancer (p=0.099) and rectal cancer (p=0.098). Similar trend of reduced RFS (p=0.072) and OS (p=0.083) was noted with HER2 negative expression in patients treated with adjuvant therapy. However, MLH1 protein expression failed to show any prognostic or predictive value. Further, significant positive correlation was observed between HER2 and MLH1 protein expression (p<0.001). In conclusion, absence of cytoplasmic HER2 protein expression could be a useful biomarker to identify high risk group of CRC patients with poor clinical outcome.


Nair CP , Gajjar KK , Vora HH and Ghosh NR

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