4.6 Article

Prognostic Impact of del(17p) and del(22q) as Assessed by Interphase FISH in Sporadic Colorectal Carcinomas

Journal

PLOS ONE
Volume 7, Issue 8, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0042683

Keywords

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Funding

  1. Consejeria de Sanidad, Junta de Castilla y Leon, Valladolid, Spain [SAN673/SA39/08, SAN/103/2011]
  2. Fundacion Memoria de Don Samuel Solorzano Barruso, Salamanca, Spain
  3. Caja de Burgos (Obra Social), Burgos, Spain
  4. Grupo Excelencia de Castilla y Leon [GR37]
  5. Red Tematica de Investigacion Cooperativa en Cancer (RTICC) from the Instituto de Salud Carlos III (ISCIII), Ministerio de Sanidad y Consumo, Madrid, Spain [PI12/02053-FIS, RD06/0020/0035-FEDER]
  6. ISCIII, Ministerio de Ciencia e Innovacion, Madrid, Spain [CP05/00321, FI08/00721]
  7. Caja de Burgos - Obra Social

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Background: Most sporadic colorectal cancer (sCRC) deaths are caused by metastatic dissemination of the primary tumor. New advances in genetic profiling of sCRC suggest that the primary tumor may contain a cell population with metastatic potential. Here we compare the cytogenetic profile of primary tumors from liver metastatic versus non-metastatic sCRC. Methodology/Principal Findings: We prospectively analyzed the frequency of numerical/structural abnormalities of chromosomes 1, 7, 8, 13, 14, 17, 18, 20, and 22 by iFISH in 58 sCRC patients: thirty-one non-metastatic (54%) vs. 27 metastatic (46%) disease. From a total of 18 probes, significant differences emerged only for the 17p11.2 and 22q11.2 chromosomal regions. Patients with liver metastatic sCRC showed an increased frequency of del(17p11.2) (10% vs. 67%; p<.001) and del(22q11.2) (0% vs. 22%; p=.02) versusnon-metastatic cases. Multivariate analysis of prognostic factors for overall survival (OS) showed that the only clinical and cytogenetic parameters that had an independent adverse impact on patient outcome were the presence of del(17p) with a 17p11.2 breakpoint and del(22q11.2). Based on these two cytogenetic variables, patients were classified into three groups: low- (no adverse features), intermediate- (one adverse feature) and high-risk (two adverse features)-with significantly different OS rates at 5-years (p<.001): 92%, 53% and 0%, respectively. Conclusions/Significance: Our results unravel the potential implication of del(17p11.2) in sCRC patients with liver metastasis as this cytogenetic alteration appears to be intrinsically related to an increased metastatic potential and a poor outcome, providing additional prognostic information to that associated with other cytogenetic alterations such as del(22q11.2). Additional prospective studies in larger series of patients would be required to confirm the clinical utility of the new prognostic markers identified.

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