ISPO

Transforming growth factor alpha: a valid surrogate endpoint biomarker?

SW Beenken, MDa, RD Hockett Jr, MDb, WF Malone, PhD, MPHc, KI Bland, MDa

aDepartment of Surgery, The University of Alabama at Birmingham, Birmingham, AL, bEli Lilly and Co., Indianapolis, IN, cDivision of Cancer Prevention, The National Cancer Institute, Bethesda, MD

To validate their use as surrogate endpoint biomarkers (SEBs), transforming growth factor alpha (TGF-alpha) and epidermal growth factor receptor (EGFr) mRNA expression were evaluated using quantitative, competitive RT-PCR in sequential biopsy specimens from patients with dysplastic oral leukoplakia (DOL) who were treated with 13-cis retinoic acid (13-CRA) in a prospective, randomized chemoprevention trial for squamous cell carcinoma of the upper aerodigestive tract (SCC). 59% of 28 treated patients showed more than 50% clearance of DOL. Using the Wilcoxon signed-rank test for paired comparisons, pre-treatment expression of TGF-alpha mRNA in DOL was significantly increased when compared with its expression in adjacent normal-appearing mucosa (p=0.003) and TGF-alpha expression in DOL was significantly reduced after 6 months of 13-CRA treatment (p=0.016). TGF-alpha shows promise for use as a SEB in chemoprevention trials, but animal studies and/or long-term human trials are required to demonstrate the correlative effect of 13-CRA on the incidence of SCC.

KEY WORDS: Transforming growth factor alpha (TGF-alpha), Epidermal growth factor receptor (EGFR), Surrogate endpoint biomarkers, Dysplastic oral Leukoplakia, 13-cis retinoic acid, Chemoprevention.

For more information, contact Samuel.Beenken@ccc.uab.edu

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Prognostic Markers.

http://www.cancerprev.org/Journal/Issues/26/101/1294/4506