Genes predictive of chemoradiotherapy response in laryngopharyngeal carcinoma

• Published in: Otolaryngology-head and neck surgery 2004-08, Vol.131 (2), p.P65-P65
• Main Authors: Ganly, Ian, Talbot, Simon, Maghami, Ellie G., Viale, Agnes, Olshen, Adam, Shah, Jatin P., Socci, Nicholas, Singh, Bhuvanesh
• Format: Article
• Language: English
• ISSN: 0194-5998; 1097-6817
• DOI: 10.1016/j.otohns.2004.06.042

Objectives: To identify angiogenesis/metastasis related genes that are predictive of locoregional failure in patients undergoing chemoradiotherapy (CRT) treatment. Methods: Tumor tissue was collected and snap-frozen from 35 sequential patients with histologically confirmed laryngopharyngeal cancer being treated with CRT. Gene expression analysis was performed on all cases using a novel cDNA array consisting of 277 genes functionally associated with angiogenesis (n = 152) and/or metastasis (n = 125). A total of 1152 randomly selected genes were used for intersample normalization. RNA was extracted from freshly frozen pretreatment biopsies, reverse transcribed, labelled using cy3 and cy5, and then hybridized onto the micro array slide. Image capture and analysis was performed using GenePix Pro 3.0. Locoregional failure was correlated to the gene expression profiles to identify genes predictive for locoregional failure. Genes were validated and quantified using real time RT-PCR. Results: Of 35 patients, locoregional failure occurred in 9. Seventeen genes correlated with locoregional failure (2 sample t test P < 0.05). Seven genes were chosen for further analysis based on the availability of commercially available antibodies for immunohistochemistry. Of these 7 genes, real time RT-PCR validated 4 genes (mdm2, VCAM-1, ERBB2 and HRAS) (Wilcoxen rank sum test; 0.008, 0.024, 0.041 and 0.035, respectively). The predictive value of these genes was further validated by immunohistochemistry on an independent set of paraffin embedded LPC from patients treated CRT. Conclusions: Genomic screening and real-time RT-PCR analyses identified and validated 4 genes predictive for locoregional failure in LPC patients treated by CRT. The role of these genes in treatment selection and the functional basis for their activity in CRT response merits further consideration.