Características diferenciales de las principales vías de carcinogénesis en el cáncer colorrectal de aparición precoz según su localización

Resumo

Worldwide, colorectal cancer (CRC) is the third most common neoplasm and the second cause of death after lung cancer. In 2018, 1.9 million new cases of CRC were registered and around 900 thousand people died from it. The risk of suffering from CRC is higher in developed countries, while the lowest rates have been observed in developing countries. CRC in young adults represents approximately the 11% of the global colon cancer and 18% of rectal cancer. The incidence at this age group has increased in recent decades, compared to that described for patients over 49 years, in whom it has decreased. In Europe, although the incidence has increased in most countries, there is great heterogeneity between them. The classical model of the adenoma-carcinoma sequence has evolved in recent years and CRC is more frequently described according to molecular features. To date, three main pathways of carcinogenesis have been described: microsatellite instability (MSI) or suppressor pathway; the chromosomal instability (INC), or mutator pathway and the serrated pathway or the CPG Island Methylator Phenotype. Tumors with MSI (10-15%) could arise through two different pathways: hereditary forms such as Lynch Syndrome (SL), whose molecular basis are mutations at the germinal level; and sporadic cases, secondary to MLH1 hypermethylation. IMS tumors are preferentially located at the right side, and histologically they are undifferentiated, mucinous and they have a high percentage of signet cells. Most sporadic tumors (80%) are made through the suppressor pathway, characterized by aneuploidy and high frequency of loss of heterozygosity (LOH). These tumors are usually located in the left colon, they are undifferentiated, and they are associated with germline mutations. The serrated pathway occurs in up to 35% of CRC. This type of tumors, which are more frequent in women, are generally undifferentiated, located in the right colon and with a high degree of hypermethylation. Carcinogenesis pathways are not mutually exclusive, there are overlaps between them, but there will be a dominant one. Taking into account this assumption and the genetic and molecular alterations of CRC, a molecular classification has been made in order to individualize the treatment. This classification establishes four differentiated groups according to MSI and CIMP status. Early onset colorrectal cancer (EOCRC) is usually associated with worse prognosis and has specific characteristics: invasive phenotype, low degree of differentiation, high mucinous component, high frequency of synchronous and/or metachronous tumors and greater familial aggregation. As for their location, there is no consensus; some studies point to a preference for the left side and others for the right. OBJECTIVES: The aim of our study is to describe the clinical-pathological, familiar and molecular characteristics of CRC in young adults according to the different carcinogenesis pathways and to find out the distinct characteristics taking into account the tumour location. In this way we will establish a colonic map in which the characteristics of EOCRC are summarized according to their location...