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

• Published in: Journal of surgical oncology Vol. 72; no. 3; pp. 167 - 174
• Main Authors: Salud, Antonieta, Porcel, José M., Raikundalia, Bhavna, Camplejohn, Richard S., Taub, Nick A.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.11.1999; Wiley-Liss
• Subjects: Adult; Aged; ATP Binding Cassette Transporter, Subfamily B, Member 1 - analysis; Biological and medical sciences; colorectal cancer; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; DNA, Neoplasm - analysis; Female; Flow Cytometry; Gastroenterology. Liver. Pancreas. Abdomen; Humans; immunohistochemistry; Male; Medical sciences; Middle Aged; Ploidies; Prognosis; prognostic factors; S Phase; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Human; Immunohistochemistry; Flow cytometry; Ploidy; Rectal disease; Prognosis; P Glycoprotein; Tumoral marker; Malignant tumor; Gene expression; Colonic disease; Cox model; DNA; S Phase; Rectum; Digestive diseases; Intestinal disease; Colon
• ISSN: 0022-4790; 1096-9098
• DOI: 10.1002/(SICI)1096-9098(199911)72:3<167::AID-JSO10>3.0.CO;2-H

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 cytometric DNA ploidy and S‐phase fraction (SPF) and P‐glycoprotein (Pgp) expression 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). DNA ploidy and SPF were evaluated by flow cytometry and Pgp by immunohistochemistry using monoclonal antibody C219. The Cox regression model was used to 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 significantly related to tumor site (P = 0.010), tumor stage (P = 0.016), and vascular invasion (P = 0.015) but not to other clinicopathologic variables. Patients with DNA diploid tumors showed a better survival rate than did those with aneuploid tumors. After stage IV disease was excluded, patients with diploid tumors also presented a better disease‐free and overall survival than did patients with aneuploid tumors. Mean SPF of the whole series was 13.5% (median = 11.3%, range = 1.4%–29.9%). Aneuploid tumors had a higher median SPF than did diploid tumors (17 vs. 6.2; P = 0.0001). SPF was only related significantly 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 IV was excluded, SPF was also an independent prognostic 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 expression had no influence on survival. Conclusions Our results suggest that flow cytometric DNA ploidy and SPF are significant and independent prognostic factors in patients with colorectal carcinoma, whereas Pgp expression is not. J. Surg. Oncol. 1999;72:167–174. © 1999 Wiley‐Liss, Inc.