MOLECULAR PROFILES IN COLORECTAL CANCER
Catarina F. Gomes*1, Ana C. Sousa2, Francisco Branco1, Carolina Palmela1, Inês Rolim3, Ana R. Henriques4, Maria Helena Oliveira1, Paula Borralho5, Jose Alberto N. Teixeira1, Sónia Velho1, Rui Maio1, Isabel Fonseca4, Marília Cravo1
1Hospital Beatriz Ângelo, Lisbon, Portugal; 2Genomed, Lisbon, Portugal; 3Instituto Português de Oncologia, Lisbon, Portugal; 4Faculty of Medicine of Lisbon, Lisbon, Portugal; 5Hospital CUF Descobertas, Lisbon, Portugal
Background: Colorectal cancer (CRC) is an heterogeneous disease with different prognosis and response to therapy. This phenotypic diversity is related with distinctive genetic pathways, such as chromosomal instability (RAS mutation), mismatch repair (MLH1, MHS2 and MSH6 deficiency) and methylador pathway (BRAF mutation). Our aim was to correlate clinical and genetic characteristics of CRC and to evaluate whether prognosis and response to therapy was related to tumor genotype. Methods: Retrospective cohort of patients operated for CRC in our hospital, from 2012 to 2014. RAS and BRAF mutations were evaluated with RT-PCR technique Idylla®. MMR deficiency was characterized by absence of MLH1, MSH6 and/or MSH2 expression, evaluated by tissue micro arrays. The overall survival (OS) and disease free survival (DFS) were assessed using survival analysis. Results: 228 patients were included (58% males, age 69,5 years [21-95], follow-up of 49 mo [0,1-78,8]). Disease stage was the following: I 20.6%, II 28.5%, III 30.7% and IV 20.2%. 85,1% (194/228) were located in the colon, of which 44% were right-sided. In non-metastatic (M0) patients, left-sided tumors had a higher mortality rate (33% vs 18,8%, p=0,04), without differences in age, gender distribution, stage or relapse rate. No differences in clinical settings were found in M1 patients. Overall, 56% (108/194) had a mutation in RAS (RASmut), 7.5% (15/194) in BRAF (BRAFmut) and 12% (17/144) were MMR deficient. In M0 patients, RASmut tumors had a lower OS compared to RASwt (57,1 vs 62,6 mo, p=0,03). BRAFmut tumors were more frequent in the right colon (13.5% vs 1.7%, p=0,001) and in females (11.5% vs 4.5%, p=0,005) but OS was similar (53 vs 50 mo,p=0,60). MMR deficient tumors were more frequent in the right colon (20,4% vs 5,9%, p=0,02), without influencing OS (47,7 vs 52,7 mo, p=0,67). DFS was not influenced by tumor location (p=0,33), RAS (p=0,12), BRAF (p=0,86) or MMR (p=0,75). In multivariate analysis, RAS mutational status (HR 2,2 [CI 95% 1,01 - 4,47], p=0,05) and tumor location (HR 2,4 [CI 95% 1,16-5,18], p=0,03) were independent predictive factor for death and relapse. In metastatic patients, right-sided tumors had lower median OS (6 vs 29 mo, p=0,27) as well as BRAFmut tumors (4 vs 29 mo, p=0,11), albeit non-significant. 74/194 M0 and 29/46 M1 patients were treated with chemotherapy. We did not find any association between molecular markers and response to therapy, both in the adjuvant or metastatic setting. Conclusions: In this cohort, 44% of tumors were located in the right colon; 56% exhibited chromosomal instability, 7.5% were BRAF mutated and 12% were MMR deficient. In non-metastatic patients, OS was longer in RASwt tumors. BRAFmut and MMR deficient tumors were more frequent in right colon without influencing OS. No association was found between molecular characteristics and response to therapy.
Back to 2019 Posters
