Feasibility analysis of mutational status of advanced colorectal cancer patients and correlation to disease progression

e14177 Background: Mutational Analyses are being increasingly performed on colorectal cancer patients. More efforts are needed to correlate this data to clinical outcomes such as disease prognosis, metastasis, and tumor responsiveness to chemotherapy or targeted therapy. We assessed the mutational status of patients diagnosed with colorectal cancer in the GI oncology clinics of Huntsman Cancer Institute. Methods: We examined 46 patients diagnosed with colorectal cancer that had molecular profiling performed. To determine effectiveness of mutation analysis we compared the time to progression (TTP) of patients in correlation to KRAS or BRAF, PIK3CA and PTEN status. KRAS, BRAF and PIK3CA testing was performed by direct sequence analysis on genomic DNA isolated from a formalin-fixed paraffin-embedded tumor sample. Testing utilized custom primers designed to flank, amplify and sequence codons 12 and 13 in exon 2 and codon 61 in exon 3 of the KRAS gene, codons 464-469 of exon 11 and codon 600 of exon 15 in the BRAF gene located at 7q34, and codons 539-546 of exon 9 and codons 1043-1049 of exon 20 in the PIK3CA gene located at 3q26.3. PTEN expression was determined by immunohistochemistry. H-score of ≤10 was considered PTEN Low. Results: Of the patients reviewed there were 26 male, 20 female with a median age of 59 (23-81). 43 patients had metastatic disease and 3 patients had localized disease. Mutations found were 48% KRAS, 6% BRAF, 13% PIK3CA, 46% PTEN Low, 13% KRAS + PIK3CA, and 28% KRAS/BRAF + PTEN Low. In patients with KRAS/BRAF wild type (n=14), median TTP from diagnosis to starting first chemotherapy for metastatic disease was 365 days as compared to KRAS/BRAF mutant (n=21) of 182 days (p=0.008). This study could not detect any correlation between dual alterations in RAS with PI3 kinase pathway and TTP probably as a function of lower sample sizes. Conclusions: Our data supports association of KRAS and BRAF mutational status to TTP rates in colorectal cancer patients. Substantial numbers of patients have alterations in the PI3-Kinase pathway in combination with the RAS pathway. Continued testing of molecular mutational status is needed in order to improve these predictive models.