Prognostic significance of DNA ploidy, S-phase fraction, and P-glycoprotein expression in colorectal cancer

Background and Objectives: Parameters that allow prediction of the disease course in colorectal cancer would aid the development of improved treatment strategies. For this reason, we evaluated the prognostic value of flow cyt ometric DNA ploidy and S-phase fraction (SPF) and P-glycoprotein (Pgp) expr ession in this type of tumor. Methods: The prognostic significance of DNA ploidy, SPF, and Pgp expression on paraffin-embedded sections from 107 patients with colorectal carcinoma was determined. The mean follow-up was 36.6 months (range = 3-72 months). D NA ploidy and SPF were evaluated by flow cytometry and Pgp by immunohistoch emistry using monoclonal antibody C219. The Cox regression model was used t o adjust for several clinical and pathologic covariates. Results: Of the 107 carcinomas examined, 44 (41.1%) were classified as DNA diploid and 63 (58.9%) as DNA aneuploid. DNA ploidy pattern was significant ly related to tumor site (P = 0.010), tumor stage (P = 0.016), and vascular invasion (P = 0.015) but not to other clinicopathologic variables. Patient s with DNA diploid tumors showed a better survival rate than did those with aneuploid tumors. After stage IV disease was excluded, patients with diplo id tumors also presented a better disease-free and overall survival than di d patients with aneuploid tumors. Mean SPF of the whole series was 13.5% (m edian = 11.3%, range = 1.4%-29.9%). Aneuploid tumors had a higher median SP F than did diploid tumors (17 vs. 6.2; P = 0.0001). SPF was only related si gnificantly with tumor location (P = 0.026). In the multivariate analysis, SPF was a significant independent prognostic factor for overall survival (P = 0.01). When stage TV was excluded, SPF was also an independent prognosti c variable for both disease-free (P = 0.02) and overall (P = 0.01) survival . Of 107 tumors, 61 (57%) were positive for Pgp expression, but no relation was found between this and other clinicopathologic parameters. Pgp express ion had no influence on survival. Conclusions: Our results suggest that flow cytometric DNA ploidy and SPF ar e significant and independent prognostic factors in patients with colorecta l carcinoma, whereas Pgp expression is not. (C) 1999 Wiley-Liss, Inc.