Toward a Molecular Classification of Synchronous Colorectal Cancer: Clinical and Molecular Characterization.
Two or more primary colorectal tumors coexisting at the time of diagnosis are considered to be synchronous tumors. It is estimated that synchronous colorectal cancer (SCRC) only accounts for 1.1% to 8.1% of all colorectal cancers (CRCs), and its molecular basis is still poorly understood.



We evaluated the microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP) statuses in a series of 49 patients (98 tumors) diagnosed with sporadic SCRC at the 12 de Octubre University Hospital with the aim of improving the molecular characterization of this type of tumor. We considered Lynch syndrome, familial adenomatous polyposis, and MUTYH-associated polyposis (MAP) as exclusion criteria.



Molecular subgrouping on the basis of MSI and CIMP enabled us to define 4 groups that corresponded to the molecular classification proposed for single-tumor CRC. We observed a significant predominance of MSI tumors at the right side regardless of the methylation pattern, and a significant prevalence of microsatellite-stable tumors either at the left side or throughout the entire colon (P = .026). Furthermore, we defined some molecular features frequently observed in sporadic SCRC such as a low-frequency of MSI (8.2%). We observed a high concordance in terms of MSI between simultaneous tumors (93.9%) and a lower concordance in terms of CIMP (51%) between such tumors.



Our findings support the hypothesis that SCRC involves an environmental rather than a genetic component in which various etiologic factors might modify tumor progression. Further studies are required to refine the molecular characterization of SCRC.
Digestive Cancer Research Group, Centre for Biomedical Research, 12 de Octubre University Hospital, Madrid, Spain.
María
M
Arriba
Digestive Cancer Research Group, Centre for Biomedical Research, 12 de Octubre University Hospital, Madrid, Spain.
Ricardo
R
Sánchez
Molecular Biology Laboratory, 12 de Octubre University Hospital, Madrid, Spain.
Daniel
D
Rueda
UGC de Laboratorios, Hospital Universitario San Agustín, Linares, Jaen, Spain.
Laura
L
Gómez
Biomedical Research Institute of Salamanca (Instituto de Investigación Biomédica de Salamanca), University Hospital of Salamanca-Universidad de Salamanca/Centro Superior de Investigaciones Científicas, Salamanca, Spain; Institute of Molecular and Cellular Biology of Cancer (Instituto de Biología Molecular y Celular del Cáncer), University of Salamanca-Centro Superior de Investigaciones Científicas, Salamanca, Spain.
Juan L
JL
García
Department of Pathology, 12 de Octubre University Hospital, Madrid, Spain.
Yolanda
Y
Rodríguez
Department of Digestive Diseases, Gregorio Marañón General University Hospital, Madrid, Spain.
José Antonio
JA
Pajares
Biomedical Research Institute of Salamanca (Instituto de Investigación Biomédica de Salamanca), University Hospital of Salamanca-Universidad de Salamanca/Centro Superior de Investigaciones Científicas, Salamanca, Spain; Institute of Molecular and Cellular Biology of Cancer (Instituto de Biología Molecular y Celular del Cáncer), University of Salamanca-Centro Superior de Investigaciones Científicas, Salamanca, Spain.
Jessica
J
Pérez
Familial Cancer Clinical Unit, Human Cancer Genetics Program, Spanish National Cancer Research Centre (Centro Nacional de Investigaciones Oncológicas), Madrid, Spain; Center for Biomedical Network Research on Rare Diseases (Centro de Investigación Biomédica en Red de Enfermedades Raras), Institute of Health Carlos III, Madrid, Spain.
Miguel
M
Urioste
Biomedical Research Institute of Salamanca (Instituto de Investigación Biomédica de Salamanca), University Hospital of Salamanca-Universidad de Salamanca/Centro Superior de Investigaciones Científicas, Salamanca, Spain; Institute of Molecular and Cellular Biology of Cancer (Instituto de Biología Molecular y Celular del Cáncer), University of Salamanca-Centro Superior de Investigaciones Científicas, Salamanca, Spain.
Rogelio González
RG
Sarmiento
Digestive Cancer Research Group, Centre for Biomedical Research, 12 de Octubre University Hospital, Madrid, Spain; Department of Surgery, 12 de Octubre University Hospital, Madrid, Spain. Electronic address: josepereag@hotmail.com.
José
J
Perea
D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability
CpG island methylator phenotype; Microsatellite instability; Promoter methylation; Synchronous colorectal cancer; Tumor location