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J Thorac Cardiovasc Surg 2003;125:246-253
© 2003 The American Association for Thoracic Surgery
General Thoracic Surgery (GTS) |
From the Departments of Surgery and Cardiothoracic Surgery (R.V.N.L., S.R.D., S.O., J.H.P., T.R.D.), Biochemistry and Molecular Biology, and Norris Comprehensive Cancer Research Center (J.M.P., D.S., J.S., K.D.D., P.V.D.), and Pathology (K.W.), University of Southern California Keck School of Medicine, Los Angeles, Calif.
Supported by National Institutes of Health/National Cancer Institute grant RO1 CA 71716 to P.V.D. and by American Cancer Society grant 58-007-43 and a STOP Cancer award to R.V.L.
Read at the Eightieth Annual Meeting of the American Association for Thoracic Surgery, Toronto, Ontario, Canada, May 3, 2000.
Received for publication May 4, 2000. Revisions requested Aug 11, 2000; revisions received Nov 20, 2001. Accepted for publication Dec 14, 2001. Address for reprints: R. V. Lord, MD, Department of Surgery, Healthcare Consultation Center, Suite 514, 1510 San Pablo St, Los Angeles CA 90033.
Objective: This study was undertaken to investigate the role of the angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor in the development and progression of Barrett esophagus and adenocarcinomas of the esophagus and gastroesophageal junction.
Methods: Vascular endothelial growth factor and basic fibroblast growth factor messenger RNA expression levels, relative to the control gene encoding ß-actin, were measured by using a quantitative reverse transcription-polymerase chain reaction method (ABI 7700 Sequence Detector system) in specimens of Barrett intestinal metaplasia (n = 16), dysplasia (n = 11), adenocarcinoma (n = l 5), and matching normal squamous esophageal tissues (n = 35). Vascular endothelial growth factor and basic fibroblast growth factor protein expression and CD31+ microvessel density were assessed by means of immunohistochemistry in 25 tissue sections that included representative areas for each of these Barrett stages.
Results: Expression levels were significantly increased in adenocarcinoma compared with in either normal squamous mucosa (P < .0001 for both genes) or intestinal metaplasia (vascular endothelial growth factor, P = .002; basic fibroblast growth factor, P < .0001). Vascular endothelial growth factor levels were also significantly higher in cancer tissues compared with dysplasia tissues (P = .024, Mann-Whitney U test). Basic fibroblast growth factor expression was also significantly increased in Barrett dysplastic mucosa compared with in intestinal metaplasia or normal esophageal mucosa. Microvessel density was generally higher in adenocarcinoma compared with in preneoplastic Barrett tissues. The pattern of vascular endothelial growth factor and basic fibroblast growth factor protein expression was similar to the messenger RNA expression pattern, with the exception that mucin-containing goblet cells stained intensely for vascular endothelial growth factor and only weak vascular endothelial growth factor staining was present in some adenocarcinomas.
Conclusions: Vascular endothelial growth factor and basic fibroblast growth factor messenger RNA expression levels are significantly upregulated in esophageal and gastroesophageal junction adenocarcinomas, suggesting a role for these angiogenic factors in the development of these cancers. Vascular endothelial growth factor and basic fibroblast growth factor messenger RNA expression levels are also increased in some Barrett esophagus tissues, with this increase occurring at an earlier stage for basic fibroblast growth factor than for vascular endothelial growth factor. Basic fibroblast growth factor protein expression pattern is similar to the messenger RNA expression pattern, but unlike the messenger RNA findings, vascular endothelial growth factor protein expression is strongest in goblet cells.
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