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Prognostic Implications of Proliferative Activity and DNA Aneuploidy in Astler-Coller Dukes Stage C Colonic Adenocarcinomas¹

Departments of Pathology [S. P. H., B. L. E., D. G. S., T. M., K. D. B.], Surgery [S. P. H.], Community Health and Preventive Medicine [L. P., J. S. C.], and the Cancer Center [L. P., J. S. C., D. G. S., K. D. B.], Northwestern University, McGaw Medical Center, Chicago, Illinois 60611

Paraffin-embedded surgical specimens from 69 patients who underwent resections of otherwise untreated Dukes stage C adenocarcinoma of the colon were examined for proliferative activity, DNA aneuploidy, DNA index, and proportion of aneuploid cells by flow cytometry. Results were correlated to clinical characteristics of the patients and to overall survival times.

DNA aneuploid tumors were identified in 60 cases (87%), diploid tumors in 9 cases (13%). The mean S-phase fraction for all cases was 17.6%, with a standard deviation (SD) of 7.8.

In univariate statistical analysis, younger patient age, lower tumor proliferative activity, DNA index 1.2, and presence of only 1–4 lymph nodes with tumor involvement were found to be significant predictors of improved patient survival. In multivariate Cox regression analysis, low tumor proliferative activity, younger patient age, and location of the tumor in the right or transverse colon were found to be significant independent predictors of increased patient survival.

When tumor proliferative activity was stratified into statistically defined subgroups, patients with tumors of low proliferative activity (S-phase < mean - 0.5 SD) had significantly longer survival than patients with tumors of moderate proliferative activity (S-phase value > mean - 0.5 SD and < mean + 0.5 SD) or high proliferative activity (S-phase > mean + 0.5 SD). These results suggest that tumor proliferative activity in Dukes C colon carcinoma may be an important biological factor in determining patient prognosis.

¹ This research was supported by Grant PDT-285 awarded by the American Cancer Society (National Office) and Grant CA 44947 awarded by the United States Department of Health and Human Services. The Northwestern University Flow Cytometry Program is additionally supported by a generous gift from the Coleman Foundation.

² To whom requests for reprints should be addressed, at Northwestern University, McGaw Medical Center, Wesley Pavilion, Room 530, 250 East Superior Street, Chicago, IL 60611.

Received 3/ 1/90. Accepted 2/20/91.

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