Identification of angiogenesis/metastases genes predicting chemoradiotherapy response in patients with laryngopharyngeal carcinoma Journal Article


Authors: Ganly, I.; Talbot, S.; Carlson, D.; Viale, A.; Maghami, E.; Osman, I.; Sherman, E.; Pfister, D.; Chuai, S.; Shaha, A. R.; Kraus, D.; Shah, J. P.; Socci, N. D.; Singh, B.
Article Title: Identification of angiogenesis/metastases genes predicting chemoradiotherapy response in patients with laryngopharyngeal carcinoma
Abstract: 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 f 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. © 2007 by American Society of Clinical Oncology.
Keywords: immunohistochemistry; cancer chemotherapy; clinical article; controlled study; human tissue; treatment response; disease-free survival; histopathology; laryngeal neoplasms; cancer radiotherapy; antineoplastic agent; genetic analysis; metastasis; neoplasm recurrence, local; gene expression; gene expression profiling; epidermal growth factor receptor 2; vascular cell adhesion molecule 1; angiogenesis; neovascularization, pathologic; immunoenzyme techniques; gene expression regulation, neoplastic; reverse transcriptase polymerase chain reaction; microarray analysis; oligonucleotide array sequence analysis; neoplasm metastasis; predictive value of tests; ras protein; real time polymerase chain reaction; dna microarray; dna primers; frozen section; statistics, nonparametric; protein mdm2; hypopharynx carcinoma; genes, neoplasm; pharyngeal neoplasms
Journal Title: Journal of Clinical Oncology
Volume: 25
Issue: 11
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2007-04-10
Start Page: 1369
End Page: 1376
Language: English
DOI: 10.1200/jco.2005.05.3397
PUBMED: 17416856
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 11" - "Export Date: 17 November 2011" - "CODEN: JCOND" - "Source: Scopus"
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MSK Authors
  1. Simon G Talbot
    26 Talbot
  2. Ellie Ghaem Maghami
    11 Maghami
  3. Shaokun Chuai
    29 Chuai
  4. Dennis Kraus
    268 Kraus
  5. Ashok R Shaha
    698 Shaha
  6. Bhuvanesh Singh
    242 Singh
  7. Iman Osman
    36 Osman
  8. Diane Carlson
    52 Carlson
  9. Eric J Sherman
    341 Sherman
  10. David G Pfister
    389 Pfister
  11. Agnes Viale
    245 Viale
  12. Ian Ganly
    431 Ganly
  13. Nicholas D Socci
    266 Socci
  14. Jatin P Shah
    722 Shah