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Danny M. Takanishi, Jr, MD; John Hart, MD; Piero Covarelli, MD; Richard Chappell, PhD; Fabrizio Michelassi, MD

Arch Surg. 1996;131(6):587-592.

Abstract
Objective
To determine whether DNA content and cellcycle kinetic characteristics in Dukes stage B colonic adenocarcinomas provide additional prognostic information in the context of clinicopathologic variables of known significance.

Design
Archival, paraffin-embedded tissue blocks from 210 Dukes B colonic adenocarcinomas were retrieved. After confirming stage, tumor cell nuclei were extracted, suspended, and stained. Cell nuclei from adjacent normal colon mucosa were used as controls.

Setting
University-based, tertiary cancer referral center.

Interventions
Samples obtained from tumors resected at our institution between 1965 and 1984 were analyzed by flow cytometry for DNA index (DI) and percentages of cells in synthesis (S) phase (%S) and in G₂ and mitosis (M) phases (%G₂M). The data were correlated with 5-year survival. Follow-up was complete in all patients to at least 5 years.

Results
Univariate analysis showed that the highest survival rates were associated with DI values near 1 and 2 (diploid and tetraploid tumors, P=.02) and the lowest %G₂M values (tumors with fewer mitoses; P=.01). Five-year survival rates also differed significantly between patients with diploid (DI<1.1) and those with aneuploid (1.1<DI<2) tumors (80% vs 64%, respectively; P=.02). Multivariate analysis revealed that race (P<.01), lymphatic or capillary microinvasion (P<.03), and ploidy (P<.05) were significantly associated with outcome. The influence of ploidy, race, and microinvasion on 5-year survival was estimated with logistic regression, and 8 subgroups of patients emerged with 5-year survival probabilities ranging from 39% for black patients with aneuploid tumors and microinvasion to 88% for white patients with diploid tumors and no microinvasion.

Conclusions
Tumor DNA content provides additional independent information that allows further refinement of our prognostic ability in patients with Dukes B colonic adenocarcinoma. This may aid in the identification of a cohort of patients who may potentially benefit from aggressive adjuvant therapy.

(Arch Surg. 1996;131:587-592)

Author Affiliations
From the Departments of Surgery (Drs Takanishi, Covarelli, and Michelassi), and Pathology (Dr Hart), The University of Chicago, Chicago, Ill; and the Departments of Statistics and Biostatistics, University of Wisconsin, Madison (Dr Chappell).

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