Comparison of KRAS Mutation, Microsatellite Instability and Histomorphologic Features in Metastatic Colorectal Carcinomas: Single Centre Experience

Öz

Aim: Microsatellite instability (MSI) and KRAS mutations change colorectal carcinoma (CRC) treatment protocols. Advanced examinations such as immunohistochemistry and polymerase chain reaction (PCR) are required to determine MSI and KRAS mutations. On the other hand, Crohn-like lymphoid reaction (CLR), tumor-infiltrating lymphocytes (TIL), tumor budding (TB), and desmoplastic response (DR) are histomorphologic features that can be determined only with routine hematoxylin-eosin (H&E) sections. Our study aimed to evaluate relationships between MSI, KRAS mutations, and histomorphologic features. It was thought that the relationships to be determined may be useful in predicting KRAS mutations and MSI by evaluating only H&E sections. Material and Method: One hundred nine metastatic CRC cases were reviewed retrospectively. Polymerase chain reaction results were obtained from the molecular pathology report archive and performed on all cases for KRAS mutation detection upon clinical request during routine pathologic examinations. MLH1, MSH2, MSH6, and PMS2 immunohistochemistry, performed on 70 cases for MSI interpretation upon clinical request during routine pathological examinations, was re-evaluated for standardization. Routine H&E sections with tumors were examined for CLR, TIL, TB, and DR according to study-specific criteria. Results: KRAS mutations were found in 35.77% (39/109), MSI in 24.28% (17/70), CLR in 32.11% (35/109), TIL in 44.95% (49/109), TB in 73.39% (80/109), DR in 84.40% (92/109) of the cases. CLR, TIL, DR, and KRAS mutations were higher in microsatellite stable (MSS) cases, and TB was higher in MSI cases. Crohn-like lymphoid reaction, TIL, DR, and MSI were higher in KRAS wild cases, and TB in KRAS mutant cases. Only the MSS-DR correlation was statistically significant. Conclusion: The MSS-DR correlation was statistically significant in our study. However, desmoplasia was determined in 92.45% of MSS cases, and was also determined in 58.82% of MSI cases. Because DR is an expected feature in tumor stroma, its guidance in terms of MSI was limited. Also, no significant relationship was found between MSI and DR in Turkish or English literature. In our study, histomorphologic features were insufficient to predict MSI and KRAS mutations. It is vital to immediately refer patients with metastases evaluated in centers without immunohistochemistry and PCR facilities to an advanced center for MSI and KRAS mutation determination diagnosing CRC, especially for treatment selection.

Anahtar Kelimeler

• colorectal cancer;
• KRAS protein;
• microsatellite instability

Kaynakça

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