F. Lambreton1, W. Ward1, J. Purchla1, N. Nweze1, N. Goel1, S. Reddy1, E. Sigurdson1, J. Farma1 1Fox Chase Cancer Center,Department Of Surgical Oncology,Philadelphia, PA, USA
Introduction: Type 2 Diabetes mellitus (DM2) is a known risk factor for the development of colorectal cancer (CRC). Although evidence suggests that patients with both CRC and DM2 have a worse prognosis, an exact pathologic mechanism has not been elucidated. Our aim was to define mutation patterns in CRC patients with DM2.
Methods: Patients who underwent molecular profiling (MP) while receiving treatment for CRC at Fox Chase Cancer Center between 2006 and 2017 were retrospectively reviewed. Patients who were tested with our in-house targeted cancer panel, Caris or Foundation One were also included. The samples were obtained from primary tumors or metastases. Relevant clinical and pathological data were also recorded.
Results: A total of 57 patients diagnosed with CRC and DM2 were identified who underwent MP. Mean age was 66 years (range=45-86). Fourteen (24.5%) patients were stage III and 19 (33.3%) were stage IV. Of these patients, 27 (47.3%) had a mutation. Mutations in P53 and APC genes were present in 10 (37%) patients each. KRAS mutation was present in 8 (29.6%) patients, while BRAF was abnormal in 2 (7.4%) patients. Other mutations found include PIK3CA in 3 (11.1%) cases, SMAD4 in 2 (7.4%), PTEN in 1 (3.7%), and STK11 in 1 (3.7%) patient. Eleven (40.7%) patients displayed microsatellite instability (MSI). The mean number of mutations per patient was 2.0 (range= 1-5). Mean overall survival for the whole cohort was 16 months.
Conclusion: Mutation rates in the genes studied in our cohort approach those previously reported by other authors in patients with CRC but without DM2. This suggests that mutation status might not be a contributing factor into the poorer prognosis observed in this cohort. Further, larger studies are needed to confirm these results.