Wielandt Ana María, Villarroel Cynthia, Hurtado Claudia, Simian Daniela, Zamorano Diego, Martínez Maripaz, Castro Magdalena, Vial María Teresa, Kronberg Udo, López-Kostner Francisco
Laboratorio de Oncología y Genética Molecular, Clínica Las Condes, Santiago, Chile,
Dirección Académica, Clínica Las Condes, Santiago, Chile.
Rev Med Chil. 2017 Apr;145(4):419-430. doi: 10.4067/S0034-98872017000400001.
Colorectal cancer (CRC) is an heterogeneous disease. Three carcinogenic pathways determine its molecular profile: microsatellite instability (MSI), chromosomal instability (CIN) and CpG island methylator phenotype (CIMP). Based on the new molecular classification, four consensus CRC molecular subtypes (CMS) are established, which are related to clinical, pathological and biological characteristics of the tumor.
To classify Chilean patients with sporadic CRC according to the new consensus molecular subtypes of carcinogenic pathways.
Prospective analytical study of 53 patients with a mean age of 70 years (55% males) with CRC, operated at a private clinic, without neoadjuvant treatment. From normal and tumor tissue DNA of each patient, CIN, MSI and CIMP were analyzed. Combining these variables, tumors were classified as CMS1/MSI-immune, CMS2/canonical, CMS3/metabolic and CMS4/mesenchymal.
CMS1 tumors (19%) were located in the right colon, were in early stages, had MMR complex deficiencies and 67% had an activating mutation of the BRAF oncogene. CMS2 tumors (31%) were located in the left colon, had moderate differentiation, absence of vascular invasion, lymphatic and mucin. CMS3 tumors (29%) were also left-sided, with absence of vascular and lymphatic invasion, and 29% had an activating mutation of the KRAS oncogene. CMS4 tumors (21%) showed advanced stages and presence of metastases.
This new molecular classification contributes to understanding the heterogeneity of tumors. It is possible to differentiate molecular subgroups of a single pathological diagnosis of adenocarcinoma, opening the door to personalized medicine.
结直肠癌（CRC）是一种异质性疾病。三种致癌途径决定了其分子特征：微卫星不稳定性（MSI）、染色体不稳定性（CIN）和CpG岛甲基化表型（CIMP）。基于新的分子分类，建立了四种共识性结直肠癌分子亚型（CMS），它们与肿瘤的临床、病理和生物学特征相关。
根据致癌途径的新共识分子亚型对智利散发性结直肠癌患者进行分类。
对53例平均年龄70岁（55%为男性）的结直肠癌患者进行前瞻性分析研究，这些患者在一家私立诊所接受手术，未接受新辅助治疗。从每位患者的正常组织和肿瘤组织DNA中分析CIN、MSI和CIMP。结合这些变量，将肿瘤分为CMS1/MSI免疫型、CMS2/经典型、CMS3/代谢型和CMS4/间充质型。
CMS1肿瘤（19%）位于右半结肠，处于早期，存在错配修复复合物缺陷，67%具有BRAF癌基因激活突变。CMS2肿瘤（31%）位于左半结肠，分化中等，无血管侵犯、淋巴和黏液。CMS3肿瘤（29%）也位于左侧，无血管和淋巴侵犯，29%具有KRAS癌基因激活突变。CMS4肿瘤（21%）显示为晚期且有转移。
这种新的分子分类有助于理解肿瘤的异质性。有可能区分腺癌单一病理诊断的分子亚组，为个性化医疗打开大门。
