KRAS Mutations Are Associated with Specific Morphologic Features in Colon Cancer
A Gunal, B Kenney, P Hui, S Kilic, R Xu, D Jain, K Mitchell, M Robert. Gulhane Military Medical School, Ankara, Turkey; Yale University School of Medicine, New Haven, CT; New York University School of Medicine, New York, NY
Background: Genetic mutations of the KRAS gene occur at an early stage in colon cancer. KRAS mutations predict resistance to anti-EGFR therapy in Stage IV disease. While histology in colon cancer has been associated with DNA mismatch repair gene mutations, no comprehensive analysis of morphological correlates for KRAS mutations exists. As it is now the standard of care to assess KRAS mutations in Stage IV colon cancer, morphological correlates could be useful in clinical practice. The aim of the current study is to correlate histological features of colon cancer with KRAS mutations.
Design: Tumor tissue from 145 colon cancer resections performed over a two year period were tested for KRAS mutations. KRAS mutation status was correlated with histological characteristics, including age, gender, tumor site, size, gross configuration, histological type, grade, mucinous component, lymphovascular invasion, extramural venous/perineural invasion, peritumoral lymphocytic response, infiltrative vs pushing growth, TNM status and overall stage. Statistical analysis was performed using Pearson chi-square and multivariate analysis.
Results: KRAS mutations were present in 55/145 cases (37.9%), consistent with reported rates. KRAS mutations were significantly associated with usual adenocarcinoma morphology (chi square p=0.055; multivariate p=0.014), peritumoral lymphocytic response (chi square p=0.028; multivariate p=0.017), T3-T4 status (chi square p=0.012; multivariate p=0.015), right colon tumors (multivariate p= 0.027), absent lymphovascular invasion (multivariate p=0.008), and metastases at the time of resection (multivariate p=0.034). No association was found between KRAS mutational status and the other factors.
|Tumor characteristics||Odds Ratio||95% CI|
|Right colon location||2.51||1.11-5.71|
|Type (usual adenocarcinoma)||8.40||1.53-45.45|
|Tumor depth T3,T4||7.52||1.48-38.17|
|Distant metastasis at presentation||3.01||1.08-8.37|
|Absent lymphovascular invasion||3.11||1.35-7.14|
|Lymphocytic response present||2.73||1.19-6.23|