PROGNOSTIC-SIGNIFICANCE OF DNA-PLOIDY IN PATIENTS WITH STAGE-II AND STAGE-III COLON-CARCINOMA - A PROSPECTIVE FLOW CYTOMETRIC STUDY

BACKGROUND. The prognostic value of flow cytometric DNA ploidy in colo rectal carcinoma has not been defined clearly. Most previous studies w ere conducted retrospectively using archival formalin fixed, paraffin embedded tumor samples. Conversely, few data on prospective studies em ploying fresh or frozen tissue specimens are available. There is gener al agreement that fresh/frozen material is more reliable than paraffin embedded tissue for DNA ploidy analysis by flow cytometry. METHODS. I n the current investigation we evaluated the prognostic significance o f nuclear DNA content in a prospective series of 191 patients with cur atively resected TNM Stage II (n = 107) or Stage III (n = 84) sporadic colon carcinomas. DNA ploidy status was assessed by flow cytometry ut ilizing multiple frozen tumor samples. Mean follow-up in surviving pat ients was 48.5 months (median, 46.9 months; range, 29-77 months). The Cox proportional hazards model was used to adjust for several clinical and pathologic covariates. RESULTS. Of the 191 carcinomas examined, 4 7 (24.6%) were classified as DNA diploid and 144 (75.4%) as DNA aneupl oid. DNA ploidy pattern was significantly related to tumor site (P < 0 .0001), histologic type (P = 0.0002), and grade of differentiation (P = 0.009), but not to other clinical and pathologic variables. Patients with DNA diploid tumors showed a better disease free (P = 0.013) and overall survival (P = 0.021) than patients with DNA aneuploid adenocar cinomas. In particular, patients with Stage II DNA diploid tumors (n = 30) had an excellent clinical outcome, with an overall 5-year surviva l rate of 97%. When patients were analyzed according to the anatomic s ite of the turner, a significant relationship between DNA ploidy statu s and disease free and overall survival was observed in the group of p atients with carcinomas of the proximal colon (n = 84) (P = 0.004 and P = 0.002, respectively), but not among patients whose tumors were sit ed distally to the splenic flexure (n = 107). In multivariate analysis , nuclear DNA content was demonstrated to be an independent prognostic variable for both disease free and overall survival. Furthermore, in the group of patients with tumors of the proximal colon, DNA ploidy pa ttern was the single most important prognostic factor. CONCLUSIONS. Ou r results confirm that flow cytometric DNA ploidy status is a signific ant and independent prognostic factor in patients with colon carcinoma . These findings may have clinical implications for the management of affected patients, especially those with Stage II disease. (C) 1997 Am erican Cancer Society.