Molecular determinants in targeted therapy for esophageal adenocarcinoma.
OBJECTIVE
Cyclooxygenase 2 (COX-2), vascular endothelial growth factor (VEGF), and epidermal growth factor receptor (EGFR) are useful biological determinants in targeted therapy for esophageal adenocarcinoma.


METHODS
Prospective analysis.


METHODS
University tertiary referral center.


METHODS
Sixteen patients with squamous mucosa and normal results of a pH study without mucosal injury (control group), 15 with Barrett esophagus (metaplasia group), and 44 with adenocarcinoma (carcinoma group).


METHODS
Biopsy specimens were obtained 3 cm above the gastroesophageal junction. Dysplastic tissue was additionally isolated from 9 of the patients in the carcinoma group. After laser-capture microdissection, quantitative real-time polymerase chain reaction was used to measure gene expression across the spectrum of the metaplasia-dysplasia-carcinoma sequence.


METHODS
Expression of COX-2, VEGF, and EGFR in each patient group.


RESULTS
Expression of both COX-2 and VEGF was significantly up-regulated in patients with metaplasia, dysplasia, and cancer compared with controls (P<.01). Expression levels of both were significantly higher in cancer than in the metaplasia group (P<.05) and increased sequentially from metaplasia to dysplasia to cancer. Expression of VEGF was significantly higher in the dysplastic tissue than in nondysplastic Barrett epithelium (P<.05). No change in expression levels of EGFR was seen in the histologic progression to esophageal adenocarcinoma.


CONCLUSIONS
Gene expression data suggest that pharmacologic inhibition of COX-2 and VEGF may be useful adjuncts in targeted therapy for esophageal adenocarcinoma.
Vallböhmer
Daniel
D
Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, USA.
Peters
Jeffrey H
JH
Kuramochi
Hidekazu
H
Oh
Daniel
D
Yang
Dong
D
Shimizu
Daisuke
D
DeMeester
Steven R
SR
Hagen
Jeffrey A
JA
Chandrasoma
Parakrama T
PT
Danenberg
Kathleen D
KD
Danenberg
Peter V
PV
DeMeester
Tom R
TR
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001706:Biopsy; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011446:Prospective Studies; D012334:RNA, Neoplasm / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; D066246:ErbB Receptors