Comparison of kras mutation, microsatellite instability and histomorphological features in metastatic colorectal carcinomas

Colorectal cancer is the third common malignancy after lung and breast cancers in terms of their incidence, and second leading cause of cancer-related deaths after lung cancers. Because of the high incidence of colorectal cancers and high mortality rates, it is important to determine prognostic parameters and to provide correct and rapid access to treatment. Crohn like lymphoid reaction (CLLR) and tumor infiltrating lymphocytes (TIL) are considered to be good prognostic factors. Desmoplastic response (DR) with an uncertain prognostic role and tumoral budding (TB) considered as poor prognostic factor are other histomorphological features evaluated in colorectal cancers. Microsatellite instability (MSI) and KRAS mutation are also important for both prognosis and treatment. MSI which caused by germline mutations of MLH1, MSH2, MSH6 and PMS2 genes, cause Lynch syndrome. MLH1 hypermethylation causes MSI and is usually observed with BRAF mutation in sporadic colorectal cancers. MSI is seen in approximately 15% of colorectal cancers and is a good prognostic factor. KRAS mutation is seen in 30-45% of colorectal cancers, causes chromosomal instability and is a poor prognostic factor. 109 patients who were diagnosed with carcinoma from colorectal resection material and examined for KRAS mutation with PCR between 2016-2019 years in Karadeniz Technical University Medicine Faculty Pathology Department, were included in our study. Immunhistochemical expressions of MLH1, MSH2, MSH6 and PMS2 were examined for MSI interpretation in 70 cases. Our aim is to evaluate the relationship between histomorphological findings (CLLR, TIL, DR, TB), MSI and KRAS mutation. We observed CLLR in 32,1% (35/109), TIL in 45% (49/109), DR in 84,4 % (92/109) and TB in 73,4% (80/109) of the patients included in our study. There were MSI in 24,2% (17/70) and KRAS mutation in 35,8% (39/109) of the cases. DR was more common in microsatellit stabile (MSS) cases and the result was statistically significant. CLLR, TIL and TB were detected more frequently in MSS cases but the results were not statistically significant. CLLR, TIL, DR and TB were detected more frequently in patients without KRAS mutations and the results were not statistically significant. KRAS mutation was found more frequently in MSS cases. MSI was found more frequently in cases without KRAS mutation. The relationship between the MSS and the presence of KRAS mutation was not statistically significant. The presence of MSI and KRAS mutations in colorectal cancers changes the prognosis and treatment protocols. Cases with MSI do not benefit from 5-Fluorouracil treatment which is classical chemotherapeutic drug but immunotherapy (Anti PD-L1drug etc.) is a treatment option. Cases with KRAS mutation have resistance to targeted therapies (Anti-EGFR drug etc.). So MSI and KRAS mutation are specially important in colorectal cancers. Where MSI and KRAS mutation evaluation can not be performed, knowing the relationship between histomorphological findings (CLLR, TIL, DR, TB), MSI and KRAS mutation, will be important for prognosis, correct and rapid access to treatment.