The prognostic value of molecular marker analysis in patients treated withtrimodality therapy for esophageal cancer

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 wit h trimodality therapy for esophageal cancer. The original pretreatment para ffin-embedded endoscopic esophageal tumor biopsy material was obtained from 118 patients treated with concurrent cisplatin + 5-fluorouracil (5-FU) + 4 5 Gy radiation followed by resection from 1986 until 1997 at the Duke Unive rsity Comprehensive Cancer Center. Three markers of possible platinum chemo therapy association [metallothionein (MT), glutathione S-transferase-pi (GS T-pi), P-glycoprotein (P-gp or multidrug resistance)] and one marker of pos sible 5-FU association [thymidylate synthase (TS)] were measured using immu nohistochemistry. The median cancer-free survival was 25.0 months, with a s ignificantly improved survival for the 38 patients who had a complete respo nse (P < 0.001), High-level expression of GST-<pi>, P-gp, and TS were assoc iated with a decreased survival. MT was not significant in this population, Multivariate analysis identified high-level expression in two of the plati num markers (GST-pi and P-gp) and the 5-FU marker TS as independent predict ors of early recurrence and death, In conclusion, this investigation measur ed 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 possib le to predict which patients may benefit most from trimodality therapy. The se data heed to he reproduced in a prospective investigation.