Classifying early-onset colorectal cancer according to tumor location: new potential subcategories to explore.
Early-onset Colorectal Cancer (ECRC) represents a significant and increasing proportion of Colorectal Cancer (CRC), but it is a heterogeneous entity that probably encompasses specific subclasses. On the premise that the carcinogenetic mechanism and progression of CRC may differ with location, we analyzed molecular and clinical characteristics of ECRC according to tumor location in order to identify more homogeneous subgroups of CRC. Right-sided ECRC is a subset in which most Lynch Syndrome cases are found, with earlier stages at diagnosis and better prognosis. At this location the CpG Island Methylator Phenotype (CIMP) is predominant and Chromosomal Instability (CI) is rare. Left-sided ECRC appears as a transitional or intermediate location, except for CI tumors, that seem to predominate at this location. Finally, rectal ECRC shows Microsatellite Stability, CIMP low-0 and low CI - with recurrent altered chromosomal regions in common with left-sided ECRC-, possibly in relation with Microsatellite And Chromosomal Stable tumors, but with an unexpected familial component and worse prognosis. All this suggest that the molecular basis of ECRC varies with tumor location, which could affect the clinical management of patients.
Department of Surgery, Hospital Universitario 12 de Octubre Madrid, Spain ; Digestive Cancer Research Group, Hospital 12 de Octubre Research Institute Madrid, Spain.
José
J
Perea
Department of Medical Oncology, Ciudad Real General Hospital Ciudad Real, Spain.
Juana M
JM
Cano
Digestive Cancer Research Group, Hospital 12 de Octubre Research Institute Madrid, Spain ; Molecular Biology Laboratory, Hospital Universitario 12 de Octubre Madrid, Spain.
Daniel
D
Rueda
Biomedical Research Institute of Salamanca (IBSAL), Hospital Universitario de Salamanca-USAL-CSIC Spain ; Institute of Molecular and Cellular Biology of Cancer (IBMCC), Universidad de Salamanca-CSIC Spain.
Juan L
JL
García
Hereditary Endocrine Cancer Group, Human Cancer Genetics Program, Spanish National Cancer Centre (CNIO) Madrid, Spain.
Lucía
L
Inglada
Digestive Cancer Research Group, Hospital 12 de Octubre Research Institute Madrid, Spain.
Irene
I
Osorio
Digestive Cancer Research Group, Hospital 12 de Octubre Research Institute Madrid, Spain.
María
M
Arriba
Biomedical Research Institute of Salamanca (IBSAL), Hospital Universitario de Salamanca-USAL-CSIC Spain ; Institute of Molecular and Cellular Biology of Cancer (IBMCC), Universidad de Salamanca-CSIC Spain.
Jessica
J
Pérez
Digestive Cancer Research Group, Hospital 12 de Octubre Research Institute Madrid, Spain.
Miriam
M
Gaspar
Department of Surgery, Hospital Universitario 12 de Octubre Madrid, Spain.
Tamara
T
Fernández-Miguel
Department of Pathology, Hospital Universitario 12 de Octubre Madrid, Spain.
Yolanda
Y
Rodríguez
Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Centre (CNIO) Madrid, Spain ; Center for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III Madrid, Spain.
Javier
J
Benítez
Biomedical Research Institute of Salamanca (IBSAL), Hospital Universitario de Salamanca-USAL-CSIC Spain ; Institute of Molecular and Cellular Biology of Cancer (IBMCC), Universidad de Salamanca-CSIC Spain.
Rogelio
R
González-Sarmiento
Center for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III Madrid, Spain ; Familial Cancer Clinical Unit, Human Cancer Genetics Program, Spanish National Cancer Centre (CNIO) Madrid, Spain.
Miguel
M
Urioste
Cpg island methylator phenotype; Early-onset colorectal cancer; chromosomal instability; microsatellite instability; tumor location