Individual tumorigenesis pathways of sporadic colorectal adenocarcinomas are associated with the biological behavior of tumors
| Autor: | Yong S. Kim, Jin C. Kim, Se J. Jang, Chang S. Yu, Gyungyub Gong, Seon Ae Roh, Seon Y. Kim, Young Keol Cho |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Cancer Research Pathology medicine.medical_specialty Genes APC Lymphovascular invasion Colorectal cancer Loss of Heterozygosity Adenocarcinoma medicine.disease_cause DNA Mismatch Repair medicine AXIN2 Humans Aged business.industry Cancer Microsatellite instability General Medicine Middle Aged medicine.disease Oncology Female Microsatellite Instability raf Kinases DNA mismatch repair Colorectal Neoplasms Carcinogenesis business |
| Zdroj: | Cancer Science. 99:1348-1354 |
| ISSN: | 1349-7006 1347-9032 |
| DOI: | 10.1111/j.1349-7006.2008.00819.x |
| Popis: | Clinicopathologic features of sporadic colorectal adenocarcinomas were compared using integrated data from 224 [corrected] patients subjected to curative resection. Individual steps in the tumorigenesis pathway, that is, adenomatosis polyposis coli (APC), Wnt-activated, base excision repair mutations, mismatch repair defects, RAF-mediated, transforming growth factor (TGF)-beta-suppressed, bone morphogenic protein (BMP)-suppressed, and p53 alterations, were examined in terms of genetic and epigenetic changes, as well as protein expression. Genetic and molecular alterations of right colon cancers were distinct from those of left colon and rectal cancers. Rectal cancers showed the attenuated phenotype of left colon cancers. Tumors most frequently displayed either TGF-beta- or BMP-suppressed alterations (81.2%), followed by RAF-mediated alterations (78.6%), and mismatch repair defects (38.4%), constituting a total of 24 integrated pathways. Tumors lacking APC mutations or carrying the RAF alteration (V600E) were frequently associated with lymphovascular invasion and lymph node metastasis (P < 0.05). Poorly differentiated or mucinous adenocarcinomas were generally associated with high level microsatellite instability, Axin2 suppression, TGF-beta1 or BMPR1A suppression, loss of heterozygosity of D18S46 or D18S474, and absence of base excision repair mutations (P < 0.0001-0.05). Early tumor recurrence was significantly correlated with lack of APC mutations (P = 0.036). Moreover, tumors that concurrently displayed APC/Wnt-activated, TGF-beta/BMP-suppressed, and p53 alterations were significantly predisposed to early recurrence (P = 0.026). Our data clearly indicate that particular steps or pathways of colorectal tumorigenesis are closely associated with characteristic clinicopathologic features that, in turn, determine biological behavior, such as tumor growth, invasion, and recurrence. |
| Databáze: | OpenAIRE |
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