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J Thorac Cardiovasc Surg 2007;133:82-87
© 2007 The American Association for Thoracic Surgery

General Thoracic Surgery

A novel biomarker for the detection of esophageal adenocarcinoma

Zane T. Hammoud, MDa,*, Sunil Badve, MDb, Romil Saxena, MDb, Kenneth A. Kesler, MDa, Karen Rieger, MDa, Linda H. Malkas, PhDc, Robert J. Hickey, PhDc

a Thoracic Surgery Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, Ind
b Department of Pathology, Indiana University School of Medicine, Indianapolis, Ind
c Department of Medicine, Indiana University School of Medicine, Indianapolis, Ind.

Read at the Thirty-second Annual Meeting of the Western Thoracic Surgical Association, Sun Valley, Idaho, June 21-24, 2006.

Received for publication June 19, 2006; revisions received August 22, 2006; accepted for publication September 5, 2006.

* Address for reprints: Zane T. Hammoud, MD, 545 Barnhill Dr, EH 215, Indianapolis, IN 46202. (Email: zhammoud{at}iupui.edu).

OBJECTIVES: Proliferating cell nuclear antigen is a component of the DNA synthesome and functions in DNA replication and repair. Our group has recently identified an acidic isoform of proliferating cell nuclear antigen, cancer-specific proliferating cell nuclear antigen, that appears to be present only in malignant tissue. We sought to determine the presence of cancer-specific proliferating cell nuclear antigen in esophageal dysplasias and invasive adenocarcinomas to assess its potential utility in discriminating malignancy.

METHODS: With a polyclonal antibody to cancer-specific proliferating cell nuclear antigen, immunohistochemical staining was performed on samples from a total of 30 patients with Barrett esophagus with varying degrees of dysplasia and 18 patients with invasive adenocarcinoma. We also performed cancer-specific proliferating cell nuclear antigen immunohistochemical staining on a commercially available tissue microarray and on specimens obtained from endoscopic biopsies. As controls, immunohistochemical staining for cancer-specific proliferating cell nuclear antigen was performed on normal esophageal tissue and immunohistochemical staining for proliferating cell nuclear antigen was performed on all specimens with a commercially available antibody.

RESULTS: Of the Barrett esophagus specimen, 14 showed no dysplasia, 8 showed low-grade dysplasia, and 8 showed high-grade dysplasia. None of these specimens stained positively for cancer-specific proliferating cell nuclear antigen. Of the 18 adenocarcinoma specimens, all stained positively for cancer-specific proliferating cell nuclear antigen. There was no significant cancer-specific proliferating cell nuclear antigen expression in normal esophageal tissue, and proliferating cell nuclear antigen expression was noted to a high degree in all tissues.

CONCLUSIONS: Cancer-specific proliferating cell nuclear antigen appears to demonstrate high specificity for esophageal adenocarcinoma. This marker therefore may prove useful in differentiating invasive cancer from high-grade dysplasia. Cancer-specific proliferating cell nuclear antigen also holds future promise as a biomarker for esophageal adenocarcinoma.

Abbreviations and Acronyms csPCNA = cancer-specific proliferating cell nuclear antigen; csPCNAab = polyclonal antibody to cancer-specific proliferating cell nuclear antigen; KLH = keyhole limpet hemacyanin; PBS = phosphate-buffered saline solution; PCNA = proliferating cell nuclear antigen


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Discussion
J. Thorac. Cardiovasc. Surg. 2007 133: 86-87. [Extract] [Full Text] [PDF]





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