Retinoic acid receptor-alpha messenger RNA expression is increased and retinoic acid receptor-gamma expression is decreased in Barrett's intestinal metaplasia, dysplasia, adenocarcinoma sequence.
BACKGROUND
Expression levels of the retinoic acid receptors (RAR-alpha, RAR-beta, and RAR-gamma) are significantly different in neoplastic tissues compared with non-neoplastic tissues for some tumors. This study investigated whether retinoic acid receptor messenger RNA (mRNA) expression levels are altered in Barrett's esophagus and Barrett's adenocarcinoma tissues.


METHODS
Relative mRNA expression levels of the RARs were quantified by using the ABI 7700 Sequence Detector (Taqman) system in Barrett's intestinal metaplasia (n = 15), dysplasia (n = 6), adenocarcinoma (n = 17), and matching normal esophagus tissues (n = 36).


RESULTS
RAR-alpha expression was significantly increased, and RAR-gamma expression was significantly decreased, at higher stages in the Barrett's sequence. There was almost complete loss of RAR-gamma expression (relative expression level < or = 1) in a majority (70%) of the dysplasia and adenocarcinoma tissues. There were significant differences in RAR-alpha and RAR-gamma expression in histopathologically normal tissues in patients with cancer versus patients without cancer. RAR-beta expression levels were significantly elevated in adenocarcinoma versus normal esophagus tissues. The RAR expression profile was similar for cancers arising within the esophagus and for cancers arising at the gastroesophageal junction.


CONCLUSIONS
RAR mRNA expression levels are significantly different in Barrett's tissues compared with normal esophagus tissues, and these levels are significantly different in Barrett's dysplasia and adenocarcinoma tissues compared with nondysplastic tissues. These results suggest that RAR mRNA levels may be useful biomarkers for this disease and that gastroesophageal junction adenocarcinomas are genetically similar to esophageal adenocarcinomas. These results also suggest that a cancer field is present in the esophagus in patients with cancer and that genetic alterations can precede histopathologic alterations in this disease.
Lord
R V
RV
Department of Surgery, University of Southern California Keck School of Medicine and USC/Norris Cancer Center, Los Angeles, Calif., USA.
Tsai
P I
PI
Danenberg
K D
KD
Peters
J H
JH
Demeester
T R
TR
Tsao-Wei
D D
DD
Groshen
S
S
Salonga
D
D
Park
J M
JM
Crookes
P F
PF
Kiyabu
M
M
Chandrasoma
P
P
Danenberg
P V
PV
D000230:Adenocarcinoma / Q000378:metabolism*; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000378:metabolism*; D004943:Esophagogastric Junction; D004947:Esophagus / Q000378:metabolism; D006801:Humans; D007422:Intestines / Q000473:pathology*; D008679:Metaplasia; D012333:RNA, Messenger / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012016:Reference Values; D000072482:Retinoic Acid Receptor alpha; D000097768:Retinoic Acid Receptor gamma
D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D000097768:Retinoic Acid Receptor gamma; C000607071:RARA protein, human