Immunohistochemical phenotype of colorectal carcinoma in patients with KRAS mutation and mismatch repair status

Abstract

Introduction: Aberrant expression of CK7/CK20/CDX2 is reported in percentage of colorectal carcinomas (CRC). Aim: The objective of this study was to investigate specific morphological and immunohistochemical characteristics of colorectal carcinoma with KRAS mutation status and microsatellite instability. Materials and methods: Seventy-one patients with CRC and examined KRAS mutation status were included in the investigation. Immunohistochemistry was performed using antibodies to CK7, CK20, CDX2, PMS2, and MSH6. An automatic immunostainer (Ventana BenchMark GX) was used following the manufacturer’ instructions. Fisher’s exact test was used for statistical analysis (p value <0.05). Results: Immunohistochemical analysis was performed for CK7, CK20, CDX2, PMS2, and MSH6. Aberrant expression of the typical immunohistochemical profile CK7/CK20/CDX2 was observed in 50% of the cases. The highest sensitivity and specificity were established for CDX2, with 93% of the cases demonstrating positive nuclear expression in the tumor cells. As for the microsatellite status, 20% of the examined colorectal cancers showed loss in expression for one or both of the mismatch repair proteins - PMS2 and MSH6, which was associated with loss of expression for CK20 and CDX2 as well. Downhill correlation was found also between CK20 expression and the presence of mutation in the gene for KRAS. Conclusions: Our results may support the heterogeneity of colorectal carcinoma. Statistically significant correlation was found between the expression of CK20 and CDX2 and microsatellite deficient and KRAS mutant colorectal cancers. This may lead to application of immunohistochemical screening panel for selection of patients with CRC for genetic testing. Further studies on large cohorts correlating different immunohistochemical profiles to molecular subtypes of colorectal carcinoma are needed for better understanding of the pathogenesis and behavior of colorectal carcinoma.