Article
Lab Invest 2001, 81:307–315
Redefining the Significance of Aneuploidy in the Prognostic Assessment of Colorectal Cancer
Rosa-Ana Risques1, Victor Moreno2, Eugenio Marcuello3, Jordi Petriz1, Jose Antonio Cancelas1, Francesc J Sancho4, Àngels Torregrosa1, Gabriel Capellà3,5 and Miguel A Peinado1
- 1Institut de Recerca Oncològica, Hospital Duran i Reynals, L'Hospitalet, Barcelona, Spain
- 2Institut Català d'Oncologia, Hospital Duran i Reynals, L'Hospitalet, Barcelona, Spain
- 3Servei d'Oncologia Médica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- 4Servei d'Anatomia Patològica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- 5Laboratori d'Investigació Gastrointestinal, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Correspondence: Dr. Miguel A. Peinado, Institut de Recerca Oncològica, Hospital Duran i Reynals, Autovia Castelldefels km 2,7, 08907 L'Hospitalet, Barcelona, Spain. E-mail: mpeinado@iro.es
Received 31 August 2000.
Abstract
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.
