Increased c-myb mRNA expression in Barrett's esophagus and Barrett's-associated adenocarcinoma.
BACKGROUND
Esophageal adenocarcinoma develops through a multistage process which is characterized histopathologically by progression from Barrett's intestinal metaplasia to Barrett's esophagus with dysplasia and ultimately to adenocarcinoma. The genetic basis of this process is increasingly well understood, but no studies have examined the role of the transcription factor c-myb in this disease.


METHODS
c-myb mRNA expression levels were measured using a quantitative reverse transcription-polymerase chain reaction (RT-PCR) method in specimens of Barrett's intestinal metaplasia (n = 16), adenocarcinoma (n = 22), matching normal squamous esophagus tissues (n = 38), and normal squamous esophagus tissues from patients without Barrett's esophagus or chronic gastroesophageal reflux disease (n = 10).


RESULTS
The median c-myb mRNA expression levels were significantly increased in Barrett's intestinal metaplasia tissues compared to normal esophagus tissues (P = 0.013) and in Barrett's-associated adenocarcinoma tissues compared to normal squamous esophagus tissues (P = 0.001). The c-myb expression levels increased progressively and significantly in histopathologically worse tissue types, with an increase from normal squamous esophagus mucosa to Barrett's intestinal metaplasia, and from Barrett's intestinal metaplasia to adenocarcinoma of the esophagus (P = 0.002). Median c-myb expression levels were also significantly higher in histologically normal squamous esophagus tissues from cancer patients compared to normal esophagus tissues from patients without cancer (P < 0.001) and a control group without evidence of Barrett's esophagus or gastroesophageal reflux disease (P = 0.003). Very high c-myb mRNA expression levels were found only in patients with cancer.


CONCLUSIONS
These findings suggest that upregulation of c-myb mRNA expression is an early event in the development of Barrett's esophagus and associated adenocarcinoma, that high c-myb mRNA expression levels may be a clinically useful biomarker for the detection of occult adenocarcinoma, and that a widespread cancer "field" effect is present in the esophagus of patients with Barrett's-associated adenocarcinoma.
Brabender
J
J
Department of Biochemistry and Molecular Biology, USC/Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA. drbrabender@cs.com
Lord
R V
RV
Danenberg
K D
KD
Metzger
R
R
Schneider
P M
PM
Park
J M
JM
Salonga
D
D
Groshen
S
S
Tsao-Wei
D D
DD
DeMeester
T R
TR
Hölscher
A H
AH
Danenberg
P V
PV
D000230:Adenocarcinoma / Q000503:physiopathology*; D000328:Adult; D000368:Aged; D001471:Barrett Esophagus / Q000503:physiopathology*; D004938:Esophageal Neoplasms / Q000503:physiopathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis
D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger