Redefining the significance of aneuploidy in the prognostic assessment of colorectal cancer.
The aberrant content of DNA, or aneuploidy, is a hallmark of tumor cells and may be associated with malignant potential. Based on the hypothesis that aneuploidy, as a form of genetic instability, results in an increased capability to generate cell heterogeneity, we investigated whether a comprehensive assessment of aneuploidy extent and degree might be a reliable indicator of tumor aggressiveness. DNA content was determined by flow cytometry in the infiltrating front of 131 paraffin-embedded primary colorectal carcinomas collected in a prospective design. Enrichment of tumor cells by sample microdissection resulted in neoplastic cell contents above 75%. An estimate of aneuploidy, the aneuploidy index (AI), was calculated as the tumor DNA content adjusted by the percentage of diploid and aneuploid cells in G0/G1. Thirty-nine tumors were diploid, 90 hyperdiploid, and 2 hypodiploid. The mean AI in aneuploid tumors was 1.20+/-0.17 and correlated with Dukes' stage and metastasis (p < 0.05). A high AI (receiver operating characteristic curve cutoff value greater than 1.14) predicted a poorer outcome in univariate (p = 0.004) and multivariate (p = 0.01) analyses. Based on these results, we postulate that aneuploidy is the molecular engine of progression in a subset of colorectal cancers, in which the AI seems to be a sensible and independent gauge of malignant potential. The AI determination may have prognostic application in colorectal cancer, especially in low-grade tumors, which might benefit from coadjuvant therapies.
Risques
R A
RA
Institut de Recerca Oncològica, Hospital Duran i Reynals, L'Hospitalet, Barcelona, Spain.
Moreno
V
V
Marcuello
E
E
Petriz
J
J
Cancelas
J A
JA
Sancho
F J
FJ
Torregrosa
A
A
Capella
G
G
Peinado
M A
MA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis
D004273:DNA, Neoplasm