Survivin, a potential biomarker in the development of Barrett's adenocarcinoma.
BACKGROUND
Survivin, a member of the inhibitor-of-apoptosis family, is reported to be overexpressed in esophageal cancer but no data are available about its status in the metaplastic/dysplastic sequence. The aim of this study was to measure survivin gene expression in normal squamous/columnar epithelium and in the various stages of development of Barrett's adenocarcinoma.


METHODS
Endoscopic biopsy or operative specimen samples from 5 tissue types were analyzed: (1) squamous epithelium from 3 cm above the gastroesophageal junction in patients with a negative pH study and no histologic injury (n = 17, pH- control); (2) antral tissue from patients with no evidence of Barrett's, dysplasia, or cancer (n = 29, antral control); (3) specialized intestinal metaplasia from patients with Barrett's esophagus (n = 16; Barrett's group); (4) low- or high-grade dysplasia (n = 12, dysplasia group), and (5) adenocarcinoma (n = 45 cancer group). After laser-capture microdissection cellular RNA was extracted from each tissue and reverse transcribed to complementary DNA. Expression levels of survivin were measured by reverse-transcription polymerase chain reaction.


RESULTS
Survivin gene expression was greater in columnar (antral) compared with squamous (pH-) control tissues (P = .03). Expression in quiescent Barrett's epithelium was similar to both control tissues. Expression levels in dysplastic epithelium were greater than in squamous control (P = .01) and Barrett's tissues (P = .04), but not higher than columnar control tissues, whereas expression in adenocarcinoma was greater than all tissues except dysplasia (P < .001).


CONCLUSIONS
Survivin expression may be a biomarker in the development of Barrett's adenocarcinoma that is able to distinguish between quiescent Barrett's, dysplastic Barrett's, and Barrett's adenocarcinoma.
Vallböhmer
Daniel
D
Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, USA.
Peters
Jeffrey H
JH
Oh
Daniel
D
Kuramochi
Hidekazu
H
Shimizu
Daisuke
D
Demeester
Steven R
SR
Hagen
Jeffrey A
JA
Chandrasoma
Parakrama T
PT
Danenberg
Kathleen D
KD
DeMeester
Tom R
TR
Danenberg
Peter
P
D000230:Adenocarcinoma / Q000209:etiology* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000150:complications* / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000209:etiology* / Q000473:pathology; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D000077022:Survivin
C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin