RESUMEN
BACKGROUND: We identify the features of multiple primary colorectal cancer (MPCC), synchronous colorectal cancer (SCRC) and metachronous colorectal cancer (MCRC), and distinguish between the cases that require a more extensive surgery and those where the parameters of SCRC might be important to prevent the development of MCRC. METHODS: We gathered up consecutive individuals with MPCC, 50 for each category, and 100 consecutive individuals diagnosed with 'single' colorectal cancer. Clinical and familiar information was obtained. We classified both SCRC and MCRC according to locations. RESULTS: MPCC were associated with polyps, both in earlier stages and as sporadic forms. SCRC located in the right colon were most frequently of the mucinous type. MCRC developed SCRC in 24%, along the entire colon, with familiar cancer antecedents. SCRC patients undergoing a total colectomy were younger, with the cancer spread throughout the entire colon and a larger number of polyps, whereas MCRC were predominantly adenomatous polyps. We found 2 risk factors for SCRC that led to the development of MCRC: rectal location and higher number of polyps. CONCLUSIONS: SCRC possibly involves more than an environmental component. MCRC appears to be the producer of polyps that evolve into cancer at different times, emphasising the idea of a genetic predisposition. Studies are required to find biomarkers that define patients with higher risk of developing MCRC within SCRC.
Asunto(s)
Pólipos del Colon/cirugía , Neoplasias Colorrectales/cirugía , Neoplasias Primarias Múltiples/cirugía , Anciano , Colectomía/métodos , Pólipos del Colon/diagnóstico por imagen , Colonoscopía , Neoplasias Colorrectales/clasificación , Neoplasias Colorrectales/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Humanos , Masculino , Neoplasias Primarias Múltiples/clasificación , Neoplasias Primarias Múltiples/diagnóstico por imagen , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND AND OBJECTIVES: Early age of onset is a marker of a possible hereditary component in colorectal cancer (CRC). We evaluated whether early age of onset is a good marker to identify Lynch syndrome, especially retrospectively, and if there is any other feature that could improve this identification. METHODS: We selected patients with CRC aged 45 years or younger from the pathological reports of three different institutions and different periods of time. Clinical information, family history, and tumor samples were obtained. Cases were classified according to mismatch repair (MMR) proficiency. RESULTS: Of 133 tumors, 22 showed microsatellite instability (MSI). In 15 MSI cases, a germline mutation in 1 of the MMR genes was identified, 7 of which were not identified before. The positive predictive value (PPV) of right colon CRC for a positive genetic MMR test is 30.6%, whereas "signet ring" cells and fulfillment Amsterdam II criteria have PPVs of 42.9% and 47.8%, respectively. Combining right-sided CRC with mucin production, with fulfilling Amsterdam II criteria, or with "signet ring" cells, PPVs are 54.5, 64.3, and 100%. The probability of the absence of a mutation when CRC is located in the left colon is 94.7%, whereas absence of aggregation for Lynch-related neoplasm has a 100% probability. CONCLUSIONS: Early age of onset is an effective method to identify retrospectively Lynch syndrome. Taking into account the location and histology features of the tumor, and the familial history of the cases, we notably increase the a priori probability of detecting a germline MMR mutation.
Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/etiología , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/genética , Reparación de la Incompatibilidad de ADN/genética , Inestabilidad de Microsatélites , Proteínas Adaptadoras Transductoras de Señales/genética , Adulto , Edad de Inicio , Biomarcadores de Tumor/genética , ADN de Neoplasias , Proteínas de Unión al ADN/genética , Femenino , Estudios de Seguimiento , Pruebas Genéticas , Mutación de Línea Germinal/genética , Humanos , Masculino , Homólogo 1 de la Proteína MutL , Proteína 2 Homóloga a MutS/genética , Proteínas Nucleares/genética , Reacción en Cadena de la Polimerasa , Valor Predictivo de las Pruebas , Estudios RetrospectivosRESUMEN
An important proportion of early-onset colorectal cancer (CRC) does not show a hereditary component with limited knowledge about its molecular basis and features. We analyzed a subset of patients with early-onset CRC and compared them with patients with late-onset CRC. We analyzed the microsatellite instability and CpG island methylator phenotype (CIMP) in both populations and classified them into four molecular subtypes. We analyzed the differential features between groups. Only 12 of 81 early-onset cases (15%) showed microsatellite instability, 10 of which (83%) were Lynch syndrome cases; microsatellite instability cases in elderly patients were sporadic. Early-onset microsatellite-stable cases showed different tumor locations and more family history of cancer than the elderly. Microsatellite instability/CIMP-high early-onset CRC was associated with Lynch syndrome, whereas the elderly cases were associated with BRAF mutations. Early-onset microsatellite-stable/CIMP-high CRCs were more frequently mucinous and right sided than elderly cases, with a high incidence of Lynch syndrome neoplasms; early-onset microsatellite stable/CIMP-low/0 differed from elderly cases in location, stages, incidence of multiple primary neoplasms, and the familial component. The clinical and familial differences observed between early- and late-onset CRC when considering the different carcinogenetic pathways underline that the age at onset criterion should be considered when classifying CRC.