J. Purchla1, W. H. Ward1, F. Lambreton1, N. Nweze1, T. Li2, N. Goel1, S. Reddy1, E. Sigurdson1, J. M. Farma1 1Fox Chase Cancer Center,Department Of Surgical Oncology,Philadelphia, PA, USA 2Fox Chase Cancer Center,Philadelphia, PA, USA
Introduction: The role of molecular profiling (MP) in the evaluation and management of colorectal adenocarcinoma continues to grow. In conjunction with standard genotyping for disease-related mutations, MP provides a genetic blueprint of the analyzed colorectal tumors. Although similar histologically, the clinical behavior and treatment of colon and rectal cancers can be quite dissimilar. The purpose of this investigation is to compare the colon and rectal MPs.
Methods: A retrospective study was performed using MP data of colorectal patients of any stage who were treated at our tertiary cancer center between 2006 and 2017, and underwent a Targeted Cancer Panel and/or specific single gene tests. Those who did not undergo molecular profiling were excluded. Demographic, clinical, and pathological data were collected and analyzed. The Wilcoxon test and Chi-square test were used for statistical analysis.
Results: 355 colon cancers underwent MP, and 66.5% had a mutation affecting 42 different genes. 126 rectal cancers underwent MP and 79.4% has a mutation affecting 45 different genes (P=0.007). In the colon group, 53.2% were male, and in the rectal group, 63.5% were male (P=0.04). Additionally, in the colon group, 80.6% were white, and in the rectal group, 89.7% were white (P=0.02). Stage IV colon cancer patients comprised 45.0% of the cohort, and stage IV rectal cancer patients comprised 48.8% (P=0.6). KRAS mutation was seen in 43.4% of colon and 46.1% of rectal (P=0.65), BRAF mutation in 11.6% of colon and 5.0% of rectal (P=0.06), P53 mutation in 57.4% of colon and 62.6% of rectal (P=0.4), APC mutation in 47.4% of colon and 58.2% of rectal (P=0.08), SMAD4 mutation in 10.0% of colon and 13.7% of rectal (P=0.3), PIK3CA mutation in 17.0% of colon and 7.3% of rectal (P=0.02), and defective mismatch repair/microsatellite instability (dMMR/MSI) in 12.6% of colon and 1.6% of rectal (P=0.0004). No mutations were seen in 33.5% of colon and 20.6% of rectal tumors, 1 mutation was seen in 20.9% of colon and 23.8% in rectal, 2 mutations were seen in 20.9% of colon and 13.5% of rectal, and 24.8% of colon and 42.1% of rectal had more than 3 mutations (P=0.0005). In colon cancer patients with mutations: 41.5% were located in the right colon, 10.9% in the transverse colon, 10.0% in the left colon, 37.6% in the sigmoid/recto-sigmoid colon, and 7 patients were unreported.
Conclusions: In colon and rectal patients who underwent MP had mutations affecting more than 40 unique genes. Colon tumors had higher rates of BRAF and PIK3CA mutation, and dMMR/MSI in comparison to rectal cancers. Based on this descriptive analysis, further investigation with a larger sample size is needed to affirm these patterns and may affect future treatment decision making.
