[Pathogenesis of colorectal carcinoma].
Identification of the adenoma-carcinoma sequence with its corresponding molecular genetic alterations has significantly increased our understanding of the pathogenesis of colorectal carcinoma (CRC). This route of carcinogenesis, hallmarked by genetic instability at the chromosomal level, is conventionally called the "suppressor pathway" because it is frequently accompanied by biallelic loss or inactivation of specific tumor suppressor genes (APC, p53 etc.). However, not all genetic alterations involved in carcinogenesis in the colon fit into this linear tumor progression model. In part, hereditary and sporadic CRC develops from a genetic instability at the DNA level (detected as microsatellite instability, MSI). This route of carcinogenesis in the colon is also termed the "mutator pathway". While familial adenomatous polyposis (FAP) is grouped into the "suppressor pathway" category, hereditary nonpolyposis colorectal cancer (HNPCC) typically follows the "mutator pathway". Whereas most MSI cancers presumably develop from colorectal adenomas, emerging evidence indicates that some MSI tumors may develop from certain hyperplastic polyps via a "serrated adenoma" (termed the "serrated pathway"). This review shall present the different ways that colon cancer can develop and illustrate the molecular alterations and morphological and clinical correlates that characterize these carcinogenesis pathways. The review shall conclude with a discussion of aspects relevant to clinical practice.
Reinacher-Schick
A
A
Medizinische Klinik, Knappschaftskrankenhaus, Ruhr-Universität Bochum.
Schmiegel
W
W
D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D003106:Colon / Q000473:pathology; D003111:Colonic Polyps / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D016153:Genes, Suppressor; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D012007:Rectum / Q000473:pathology
D004273:DNA, Neoplasm