Surface expression of minichromosome maintenance proteins provides a novel method for detecting patients at risk for developing adenocarcinoma in Barrett's esophagus.
OBJECTIVE
The purpose is to determine whether a novel cell cycle marker, minichromosome maintenance protein 2 (Mcm2), predicted esophageal adenocarcinoma (AC) risk in Barrett's esophagus (BE) and whether this could be used in combination with a surface sampling method.


METHODS
Archival specimens [30 normal squamous esophagus (NE), 20 gastric antrum (GA), 13 duodenum (D2), 62 BE +/- dysplasia, and 16 (AC)] were stained for Mcm2. Sequential biopsies from nine patients who developed AC during surveillance were compared with 18 matched controls who did not progress. Prospective endoscopic cytological brushings (61 NE, 90 BE +/- dysplasia, and 11 AC) were scored as Mcm2 positive or negative.


RESULTS
Mcm2 was not expressed on the luminal surface of NE, GA, and D2. In BE, the percentage of surface cells expressing Mcm2 correlated highly with the degree of dysplasia (P < 0.0001). In patients who developed AC, biopsies before dysplasia had higher Mcm2 expression than the matched control patients (mean, 28.4 and 3.4% positive cells, respectively, P < 0.0001). In the prospective cohort, the histopathological diagnosis of dysplasia or AC and the Mcm2-positive brushings were concordant in 91% of the patients (P < 0.005), and the results correlated with the frequency of cases with surface expression of Mcm2 in the retrospective study (P < 0.0001).


CONCLUSIONS
Surface expression of Mcm2 can be used to detect dysplasia and AC, as well as patients with BE at risk for subsequent development of dysplasia and AC. A brushing technique combined with Mcm2 staining has the potential to be exploited in surveillance and screening protocols.
Sirieix
Pierre S
PS
Medical Research Council-Cancer Cell Unit, Hutchison Medical Research Council Research Centre, Cambridge CB2 2XZ, United Kingdom.
O'Donovan
Maria
M
Brown
John
J
Save
Vicki
V
Coleman
Nicholas
N
Fitzgerald
Rebecca C
RC
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism; D001471:Barrett Esophagus / Q000150:complications*; D016022:Case-Control Studies; D018450:Disease Progression; D004724:Endoscopy; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D006801:Humans; D064111:Minichromosome Maintenance Complex Component 2; D009687:Nuclear Proteins / Q000096:biosynthesis*; D011230:Precancerous Conditions / Q000175:diagnosis; D011446:Prospective Studies; D012189:Retrospective Studies; D012306:Risk
D009687:Nuclear Proteins; D064111:Minichromosome Maintenance Complex Component 2