Unfavourable expression of pharmacologic markers in mucinous colorectal cancer

• Published in: British journal of cancer Vol. 92; no. 2; pp. 259 - 264
• Main Authors: GLASGOW, S. C, YU, J, CARVALHO, L. P, SHANNON, W. D, FLESHMAN, J. W, MCLEOD, H. L
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 31.01.2005
• Subjects: Adenocarcinoma, Mucinous - metabolism; Adenocarcinoma, Mucinous - mortality; Adenocarcinoma, Mucinous - pathology; Aged; Biological and medical sciences; Biomarkers, Tumor - analysis; Camptothecin - analogs & derivatives; Camptothecin - pharmacology; Clinical Study; Colorectal cancer; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Disease-Free Survival; DNA Primers; Drug Resistance, Neoplasm - genetics; Female; Fluorouracil - pharmacology; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Irinotecan; Male; Medical sciences; Organoplatinum Compounds - pharmacology; Oxaliplatin; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Antineoplastic agent; adjuvant chemotherapy; Rectal disease; Colorectal cancer; Adjuvant treatment; Biological marker; Isomerases; Cancerology; Oxaliplatin; colorectal neoplasms; Intestinal disease; messenger ribonucleic acid; Platinum II Complexes; Fluorouracil; Enzyme; Fluoropyrimidine derivatives; Transferases; DNA topoisomerase; Enzyme inhibitor; Malignant tumor; Thymidylate synthase; Colonic disease; 5-fluorouracil; Irinotecan; pharmacogenomics; Antimetabolic; Methyltransferases; Digestive diseases; Pyrimidine derivatives; Mucinous adenocarcinoma
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6602330

Patients with mucinous colorectal cancer generally have worse prognoses than those with the nonmucinous variety. The reason for this disparity is unclear, but may result from a differential response to adjuvant chemotherapy. We examined known molecular markers for response to common chemotherapy in these two histological subtypes. In all, 21 patients with mucinous and 30 with nonmucinous Dukes C colorectal cancer were reviewed for demographic data and outcome. Total RNA from the tumours and adjacent normal mucosa was isolated and reverse transcribed. Quantitative expression levels of drug pathway genes were determined using TaqMan RT-PCR (5-fluorouracil (5-FU): TYMS, DPYD, ECGF1; oxaliplatin: GSTP1 (glutathione S-transferase pi), ERCC1 and 2; irinotecan: ABCB1, ABCG2, CYP3A4, UGT1A1, CES2, TOP1). Mucinous tumours significantly overexpressed both TYMS and GSTP1 relative to nonmucinous tumours and patient-matched normal mucosa. No significant differences in expression of the remaining markers were found. Mean follow-up was 20 months; 17 patients had recurrent disease. Among patients receiving 5-FU, those with mucinous tumours experienced shorter disease-free survival (DFS) than those with nonmucinous tumours (median DFS 13.8 vs 46.5 months, P=0.053). Mucinous colorectal cancer overexpresses markers of resistance to 5-FU and oxaliplatin. Likewise, DFS may be decreased in patients with mucinous tumours who receive 5-FU. The presence of mucin should be carefully evaluated in developmental trials of new agents for treating colorectal cancer.