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Surface Expression of Minichromosome Maintenance Proteins Provides a Novel Method for Detecting Patients at Risk for Developing Adenocarcinoma in Barrett’s Esophagus

Medical Research Council-Cancer Cell Unit, Hutchison Medical Research Council Research Centre, Cambridge CB2 2XZ [P. S. S., J. B., N. C., R. C. F.], and Department of Histopathology, Addenbrooke’s Hospital, Cambridge CB2 2QQ [M. O., V. S., N. C.], United Kingdom

Purpose: 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.

Experimental Design: 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.

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