A novel biomarker for the detection of esophageal adenocarcinoma.
OBJECTIVE
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.
Hammoud
Zane T
ZT
Thoracic Surgery Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, Ind, USA. zhammoud@iupui.edu
Badve
Sunil
S
Saxena
Romil
R
Kesler
Kenneth A
KA
Rieger
Karen
K
Malkas
Linda H
LH
Hickey
Robert J
RJ
D000230:Adenocarcinoma / Q000737:chemistry / Q000175:diagnosis*; D001471:Barrett Esophagus / Q000175:diagnosis / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis*; D003937:Diagnosis, Differential; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000175:diagnosis*; D004947:Esophagus / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D011230:Precancerous Conditions / Q000175:diagnosis / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*; D020033:Protein Isoforms
D015415:Biomarkers; D018809:Proliferating Cell Nuclear Antigen; D020033:Protein Isoforms