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Identification of Angiogenesis/Metastases Genes Predicting Chemoradiotherapy Response in Patients With Laryngopharyngeal Carcinoma

Ian Ganly, Simon Talbot, Diane Carlson, Agnes Viale, Ellie Maghami, Iman Osman, Eric Sherman, David Pfister, Shaokun Chuai, Ashok R. Shaha, Dennis Kraus, Jatin P. Shah, Nicholas D. Socci, Bhuvanesh Singh

From the Laboratory of Epithelial Cancer Biology; Head and Neck Service, Department of Surgery Department of Pathology; Microarray Core Facility; Department of Medical Oncology; Department of Epidemiology and Biostatistics; and the Department of Computational Biology, Memorial Sloan-Kettering Cancer Center, New York, NY

Address reprint requests to Bhuvanesh Singh, MD, PhD, Laboratory of Epithelial Cancer Biology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021; e-mail: singhb{at}mskcc.org

Purpose: To identify genes related to angiogenesis/metastasis that predict locoregional failure in patients with laryngopharyngeal cancer (LPC) undergoing chemoradiotherapy (CRT) treatment.

Methods: Tumor tissue was collected and snap-frozen from 35 sequential patients with histologically confirmed LPC being treated with CRT. Gene expression analysis was performed using a novel cDNA array consisting of 277 genes functionally associated with angiogenesis (n = 152) and/or metastasis (n = 125). Locoregional response was correlated to the gene expression profiles to identify genes associated with outcome. These genes were internally validated by real-time reverse transcriptase polymerase chain reaction (RT-PCR) and validated externally by immunohistochemistry analysis on an independent set of patients.

Results: Locoregional failure occurred in nine of 35 patients. Seventeen genes from the cDNA microarray correlated with locoregional failure (two-sample t test, P < .05). Seven genes were chosen for additional analysis based on the availability of antibodies for immunohistochemistry. Of these seven genes, real-time RT-PCR validated four genes: MDM2, VCAM-1, erbB2, and H-ras (Wilcoxon rank sum test, P = .008, .02, .04, and .04, respectively). External validation by immunohistochemistry confirmed MDM2 and erbB2 as being predictive of locoregional response. Controlling for stage of disease, positivity for MDM2 or erbB2 was an independent negative predictor of locoregional disease-free survival.

Conclusion: Genomic screening by cDNA microarray and validation internally by real-time RT-PCR and externally by immunohistochemistry have identified two genes (MDM2 and erbB2) as predictors of locoregional failure in LPC patients treated with CRT. The role of these genes in treatment selection and the functional basis for their activity in CRT response merit additional consideration.

Presented at the Annual Meeting of the American Association for Cancer Research, March 27-31, 2004, Orlando, FL.

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

This article has been cited by other articles:

				B. Singh and D. G. Pfister Individualized Treatment Selection in Patients With Head and Neck Cancer: Do Molecular Markers Meet the Challenge? J. Clin. Oncol., July 1, 2008; 26(19): 3114 - 3116. [Full Text] [PDF]