Role of Conventional Chemosensitivity Test and
Tissue Biomarker Expression in Predicting
Response to Treatment of Peritoneal
Carcinomatosis From Colon Cancer
Chiara Arienti,
1
Anna Tesei,
1
Giorgio Maria Verdecchia,
2
Massimo Framarini,
2
Salvatore Virzì,
3
Antonio Grassi,
3
Emanuela Scarpi,
1
Livia Turci,
1
Rosella Silvestrini,
1
Dino Amadori,
1
Wainer Zoli
1
Abstract
Peritoneal carcinomatosis (PC) is observed in approximately 10% of patients with colorectal cancer at the
time of primary cancer resection. Most of these patients receive 5-fluorouracil (5-FU)- or oxaliplatin-contain-
ing chemotherapy regimens as first-, second-, or third-line treatment. In the present study, sensitivity and
resistance to drugs used to treat PC were better defined by a conventional chemosensitivity test than by
biomarker expression.
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.
Clinical Colorectal Cancer, Vol. 12, No. 2, 122-7 © 2013 Elsevier Inc. All rights reserved.
Keywords: Colon cancer, ERCC1, In vitro chemosensitivity test, Peritoneal carcinomatosis, Response prediction, TS
Introduction
Colorectal cancer is the second leading cause of cancer death in
North America and Western Europe.
1
The advent of new, effective
chemotherapeutic agents in clinical practice has increased median
survival by up to 20 months in advanced disease. This result, how-
ever, is not obtainable in patients with peritoneal carcinomatosis
(PC), which despite advances in the early detection of the primary
tumor, is still observed in approximately 10% of patients at the time
1
Biosciences Laboratory, IRCCS Istituto Scientifico Romagnolo per lo Studio e la
Cura dei Tumori (IRST), Meldola, Italy
2
Department of Surgery and Advanced Cancer Therapies, Morgagni-Pierantoni
Hospital, Forlì, Italy
3
Department of Surgery, Bentivoglio Hospital, Bologna, Italy
Submitted: Jul 25, 2012; Revised: Oct 2, 2012; Accepted: Nov 26, 2012; Epub: Jan
16, 2013
Address for correspondence: Wainer Zoli, PhD, IRCCS Istituto Scientifico Romagnolo
per lo Studio e la Cura dei Tumori (IRST), via Maroncelli 40, 47014 Meldola (FC), Italy
Fax: +39-0543-739221; e-mail contact: w.zoli@irst.emr.it
Original Study
122 Clinical Colorectal Cancer June 2013
1533-0028/$ - see frontmatter © 2013 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.clcc.2012.11.006