Identification of angiogenesis/metastases genes predicting chemoradiotherapy response in patients with laryngopharyngeal carcinoma.
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.
Ganly
Ian
I
Laboratory of Epithelial Cancer Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Talbot
Simon
S
Carlson
Diane
D
Viale
Agnes
A
Maghami
Ellie
E
Osman
Iman
I
Sherman
Eric
E
Pfister
David
D
Chuai
Shaokun
S
Shaha
Ashok R
AR
Kraus
Dennis
D
Shah
Jatin P
JP
Socci
Nicholas D
ND
Singh
Bhuvanesh
B
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
D017931:DNA Primers