Role of Conventional Chemosensitivity Test and Tissue Biomarker Expression in Predicting Response to Treatment of Peritoneal Carcinomatosis From Colon Cancer
ChiaraArienti, AnnaTesei, Giorgio Maria Verdecchia, Massimo Framarini, Salvatore Virzì, Antonio Grassi, Emanuela Scarpi, Livia Turci, Rosella Silvestrini, Dino Amadori, Wainer Zoli
Abstract
Background - 5-Fluorouracil- or oxaliplatin-based regimens are the treatments of choice in patients with PC from colon cancer. There are currently no useful preclinical evaluations to guide the decision-making process for tailored therapy. The aim of the present study was to compare the advantages and limits of a conventional in vitro chemosensitivity test with those of a panel of biomolecular markers in predicting clinical response to different drugs used to treat colon cancer-derived PC.
Patients and Methods - Fresh surgical biopsy specimens were obtained from 28 patients with peritoneal carcinomatosis from colon cancer. TS, TP, DPD, MDR1, MRP-1, MGMT, BRCA1, ERCC1, GSTP1, and XPD gene expression levels were determined by real-time reverse transcription polymerase chain reaction. An in vitro chemosensitivity test was used to define a sensitivity or resistance profile to the drugs used to treat each patient.
Results - Expression levels of the genes analyzed were generally poorly related to each other. TS and ERCC1 expression was inversely related to response to 5-FU-and/or oxaliplatin-containing regimens. Significant predictivity in terms of sensitivity but poor predictivity of resistance (56.2%) (P = .037) were observed for ERCC1 expression (90%), and high predictivity of resistance (100%) but very low predictivity of sensitivity (40%) (P = .014) were registered for TS. The best overall and significant predictivity was observed for chemosensitivity test results (62.5% sensitivity and 89% resistance; P = .005).
Conclusions - Sensitivity and resistance to drugs used in vivo was better defined by the chemosensitivity test than by biomarker expression.