Immunohistochemical assay for detection of K-ras protein expression in metastatic colorectal cancer.

BACKGROUND The monoclonal antibodies (mAbs) that target the epidermal growth factor receptor (EGFR) had expanded the range of treatment options for metastatic colorectal cancer. However, such type of treatment was shown to be ineffective if there is K-ras mutation. In most previous studies K-ras gene mutation was mainly assessed by PCR. AIM Our work is designed to detect K-ras protein expression by immunohistochemistry (IHC) aiming to reach a preliminary method that could be confirmed by PCR and considered an alternative way for the detection of K-ras aberration. We are also aiming to find a relation between K-ras protein expression and K-ras gene mutation. MATERIALS AND METHODS Paraffin embedded tissue samples from 26 metastatic colorectal cancer (mCRC) patients were analyzed for K-ras protein expression by IHC using Rap1A polyclonal antibody. Staining patterns were subjectively assessed and correlated with clinicopathological features. The results were statistically evaluated using the Chi-square test. RESULTS K-ras cytoplasmic positivity was observed in 42.3% of cases. The positivity was either strong in 26.9% or moderate in 15.4%. With respect to adenocarcinoma variants, 50% of cases were positive for K-ras protein expression while all mucinous and signet ring types were negative. The positivity was noted in 50% of moderately differentiated GII colorectal carcinomas as compared with 38.9% in poorly differentiated GIII. Positive staining was observed in 40% of cases with positive lymph node metastasis while in the absence of nodal metastasis the positivity was 45.5%. No significant correlation was found between clinicopathological parameters and K-ras staining results. CONCLUSION IHC may compliment PCR in the detection of K-ras mutation.