Abstract 3943: Determination of the molecular profile of Chilean patients with sporadic colorectal cancer

Abstract

Introduction: Colorectal cancer (CRC) represents a major health problem worldwide, ranking third among the most frequent cancers and fourth in cancer mortality. In Chile CRC is the third leading cause of cancer death. CRC is a heterogeneous disease, and three carcinogenic pathways have been described to determine the molecular profile: The microsatellite instability (MSI), chromosomal instability (CIN) and methylator phenotype (CIMP). Several studies have tried to propose CRC molecular subgroups based on the 3ways described above since CIN, MSI and CIMP are not mutually exclusive and overlapping of the 3 ways is still unclear. The most recent subtyping of CRC was in 2015, where four molecular subtypes consensus (CMS 1 to 4) were established according to clinicopathological features, molecular pathways involved and mutational status of KRAS, BRAF and PI3KCA genes in order to encourage clinical translation. 21% of tumors failed to be categorized into these subtypes. This classification allows us to understand and determine the clinical, pathological and biological characteristics of CCR to provide customized therapies to patients. Aim: To describe the molecular profile of carcinogenic pathways CIN, MSI CIMP in Chilean patients with sporadic CRC. Material and Methods: Prospective analytical study of 56 patients operated between 2010-2016 at Clinica Las Condes, without neo-adjuvant treatment. DNA was extracted from normal and tumor tissue of each patient and using PCR amplification of several markers CIN, MSI and CIMP were defined. By combining the 3 variables analyzed, tumors were classified in Group-A (MSI-high), Group-B (MSI-low / CIMP-high / CIN-high), Group-C (MSI-low / CIMP-high / CIN-low), Group-D (MSI-low / CIMP-low / CIN-high) and Group-E (MSI- neg / CIMP-neg / CIN-neg). Results: In this study, tumors in Group-A (17%) are located on the right side in patients older than 60 years and early stages. Tumors Group-B / C (18,9%) occur in patients older than 60 years and BMI>25 kg / m2, with wall invasion pT3-T4 and late stages. Tumors of Group-D / E (54,7%) are the most frequent, located on the left side, without vascular invasion and moderately differentiated. Conclusions: This study allowed to classify Chilean patients in 3 subgroups considering the 3 main routes described for carcinogenesis development: CIN, MSI and CIMP, which are consistent with the percentages described by the global consortium. Studies that analyze MSI and CIMP or MSI and CIN have consistently shown that patients with MSI-high tumors have a better prognosis (in our case 17%). Despite therapeutic advances based on this molecular characterization, both the heterogeneity of tumors and the different combinations of pathways involved have shown that the response to therapy varies depending on the individual profile of each patient, therefore in clinical practice it would be important to establish that profile for each of them. Fondecyt 1140012 Citation Format: Ana Maria Wielandt, Cynthia Villarroel, Claudia Hurtado, Daniela Simian, Diego Zamorano, Maripaz Martinez, Magdalena Castro, Maria Teresa Vial, Udo Kronberg, Francisco Lopez-Kostner. Determination of the molecular profile of Chilean patients with sporadic colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3943. doi:10.1158/1538-7445.AM2017-3943

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