A novel biomarker for the detection of esophageal adenocarcinoma

• Published in: The Journal of thoracic and cardiovascular surgery Vol. 133; no. 1; pp. 82 - 87
• Main Authors: Hammoud, Zane T., MD, Badve, Sunil, MD, Saxena, Romil, MD, Kesler, Kenneth A., MD, Rieger, Karen, MD, Malkas, Linda H., PhD, Hickey, Robert J., PhD
• Format: Journal Article
• Language: English
• Published: United States Mosby, Inc 2007; AATS/WTSA
• Subjects: Adenocarcinoma - chemistry; Adenocarcinoma - diagnosis; Barrett Esophagus - diagnosis; Barrett Esophagus - metabolism; Biomarkers - analysis; Cardiothoracic Surgery; Diagnosis, Differential; Esophageal Neoplasms - chemistry; Esophageal Neoplasms - diagnosis; Esophagus - metabolism; Humans; Immunohistochemistry; Precancerous Conditions - diagnosis; Precancerous Conditions - metabolism; Proliferating Cell Nuclear Antigen - analysis; Protein Isoforms; PBS; phosphate-buffered saline solution; proliferating cell nuclear antigen; PCNA; polyclonal antibody to cancer-specific proliferating cell nuclear antigen; KLH; 7; keyhole limpet hemacyanin; csPCNAab; csPCNA; cancer-specific proliferating cell nuclear antigen
• ISSN: 0022-5223; 1097-685X
• DOI: 10.1016/j.jtcvs.2006.09.011

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.