Prognostic Impact of del(17p) and del(22q) as assessed by interphase FISH in sporadic colorectal carcinomas.
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.


RESULTS
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
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.
Servicio General de Citometría, Departamento de Medicina and Centro de Investigación del Cáncer, IBMCC-CSIC/USAL, Hospital Universitario de Salamanca-IBSAL, Universidad de Salamanca, Salamanca, Spain.
María
M
González-González
Luís
L
Muñoz-Bellvis
Carlos
C
Mackintosh
Celia
C
Fontanillo
M Laura
ML
Gutiérrez
M Mar
MM
Abad
Oscar
O
Bengoechea
Cristina
C
Teodosio
Emilio
E
Fonseca
Manuel
M
Fuentes
Javier
J
De Las Rivas
Alberto
A
Orfao
José María
JM
Sayagués
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056905:Chromosome Breakpoints; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase / Q000235:genetics*; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015203:Reproducibility of Results; D016019:Survival Analysis