Background: Although DNA flow cytometry has been shown to be of independent value in determining the prognosis of colorectal carcinoma, a number of well-designed studies with contradictory findings have left unresolved the clinical significance of DNA ploidy and proliferation in biologically meaningful subsets of colorectal carcinoma cases.
Methods: To evaluate the prognostic significance of DNA ploidy and proliferation as determined by flow cytometry in a prospective series of 309 human colorectal carcinomas with 4-6 years of follow-up, fresh tumors were mechanically dissociated into whole cell suspensions and dual fluorescence-labeled to allow gated analysis of subpopulations with phenotypic markers. Software programs with histogram-dependent algorithms employing background, aggregate, and debris correction were used in DNA and cell cycle quantitation. Data were analyzed according to recommendations of the 1992 DNA Flow Cytometry Consensus Conference.
Results: None of the clinical, site, or staging parameters, including TNM stage variables, correlated with any flow cytometric DNA ploidy or proliferation measurement. Tumors classified as DNA aneuploid or tetraploid, by any definition, did not differ in prognosis or correlate with stage or any pathologic parameter. Univariate Kaplan-Meier survival analysis showed prognostic significance of the following: Dukes staging, individual components of TNM stage (tumor depth, lymph node status, and metastasis), vascular invasion, histologic pattern of tumor infiltration, and peritumoral lymphocytic inflammation. DNA ploidy status and proliferation measurements were not predictive of survival for the overall group or within any particular stage. Only Dukes Stage D (metastasis), vascular invasion, and depth of invasion (T classification) were significant independent predictors of survival in multivariate Cox regression models.
Conclusions: In this analysis, DNA ploidy and proliferation measurements were not predictive of survival in any stage of colorectal carcinoma. However, clinical and pathologic documentation of staging and select histopathologic observations were significant predictors of survival in univariate and multivariate analyses.