title: Identification of angiogenesis/metastases genes predicting chemoradiotherapy response in patients with laryngopharyngeal carcinoma.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Epithelial Cancer Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Ganly
authors.forename: Simon
authors.initials: S
authors.lastname: Talbot
authors.forename: Diane
authors.initials: D
authors.lastname: Carlson
authors.forename: Agnes
authors.initials: A
authors.lastname: Viale
authors.forename: Ellie
authors.initials: E
authors.lastname: Maghami
authors.forename: Iman
authors.initials: I
authors.lastname: Osman
authors.forename: Eric
authors.initials: E
authors.lastname: Sherman
authors.forename: David
authors.initials: D
authors.lastname: Pfister
authors.forename: Shaokun
authors.initials: S
authors.lastname: Chuai
authors.forename: Ashok R
authors.initials: AR
authors.lastname: Shaha
authors.forename: Dennis
authors.initials: D
authors.lastname: Kraus
authors.forename: Jatin P
authors.initials: JP
authors.lastname: Shah
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Socci
authors.forename: Bhuvanesh
authors.initials: B
authors.lastname: Singh
mesh_terms: D017931:DNA Primers; D018572:Disease-Free Survival; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D046228:Microarray Analysis; D009362:Neoplasm Metastasis / Q000235:genetics*; D009364:Neoplasm Recurrence, Local; D009389:Neovascularization, Pathologic / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010610:Pharyngeal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric
chemical_list: D017931:DNA Primers