The Prognostic Value of Molecular Marker Analysis in Patients Treated with Trimodality Therapy for Esophageal Cancer

• Published in: Clinical cancer research 2001-03, Vol.7 (3), p.562-569
• Main Authors: HARPOLE, David H, MOORE, Mary-Beth, HERNDON, James E, ALOIA, Thomas, D'AMICO, Thomas A, SPORN, Thomas, PARR, Allyson, LINOILA, Ilona, ALLEGRA, Carmen
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adult; Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; ATP-Binding Cassette, Sub-Family B, Member 1 - biosynthesis; Biological and medical sciences; Biopsy; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cisplatin - administration & dosage; Disease-Free Survival; Esophageal Neoplasms - diagnosis; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - therapy; Esophagus; Fluorouracil - administration & dosage; Gastroenterology. Liver. Pancreas. Abdomen; Glutathione S-Transferase pi; Glutathione Transferase - biosynthesis; Humans; Immunohistochemistry; Isoenzymes - biosynthesis; Medical sciences; Metallothionein - biosynthesis; Middle Aged; Multivariate Analysis; Prognosis; Proportional Hazards Models; Thymidylate Synthase - biosynthesis; Time Factors; Treatment Outcome; Tumors
• ISSN: 1078-0432; 1557-3265

The purpose of this study was to define the prognostic value of a group of molecular tumor markers in a well-staged population of patients treated with trimodality therapy for esophageal cancer. The original pretreatment paraffin-embedded endoscopic esophageal tumor biopsy material was obtained from 118 patients treated with concurrent cisplatin + 5-fluorouracil (5-FU) + 45 Gy radiation followed by resection from 1986 until 1997 at the Duke University Comprehensive Cancer Center. Three markers of possible platinum chemotherapy association [metallothionein (MT), glutathione S -transferase-π (GST-π), P-glycoprotein (P-gp or multidrug resistance)] and one marker of possible 5-FU association [thymidylate synthase (TS)] were measured using immunohistochemistry. The median cancer-free survival was 25.0 months, with a significantly improved survival for the 38 patients who had a complete response ( P < 0.001). High-level expression of GST-π, P-gp, and TS were associated with a decreased survival. MT was not significant in this population. Multivariate analysis identified high-level expression in two of the platinum markers (GST-π and P-gp) and the 5-FU marker TS as independent predictors of early recurrence and death. In conclusion, this investigation measured three possible markers associated with platinum and one possible marker associated with 5-FU in a cohort of esophageal cancer patients. Independent prognostic significance was observed, which suggests that it may be possible to predict which patients may benefit most from trimodality therapy. These data need to be reproduced in a prospective investigation.