Expression of estrogen receptor-beta isoforms in Barrett's metaplasia, dysplasia and esophageal adenocarcinoma.

We have previously shown that the majority of esophageal adenocarcinomas (EA), and its precursor Barrett's metaplasia (BM), express estrogen receptor beta (ER-B). Several isoforms of ER-B have been described and are presumed to have different functions, but their distribution in BM and EA is not known. The aim of this work was to determine which ER-B isoforms are expressed in EA and BM. Sections of formalin-fixed and paraffin-embedded esophageal tissue from 33 esophageactomy specimens, of which 27 had invasive EA, were stained for the ER-B isoforms ER-B1, ER-B2, ER-B3 and ER-B5 utilizing the immunoperoxidase method ER-B1 was detected in 23 out of 27 (85%) EA compared to 3 out of 14 (21%) Barrett's metaplasia negative for dysplasia (BMND) (p =0. 0001); ER-B2 was expressed in 22 out of 27 (81%) EA in contrast to 3 out of 14 (21%) BMND (p=0.0004); ER-B3 was positive in 27 out of 27 (100%) EA in contrast to only 1 out of 14 (7%) BMND (p<0001); ER-B5 was detected in 27 out of 27 (100%) EA compared to 9 out of 14 (62%) of BMND (p=0.0027). High- and low-grade dysplasia showed a similar ER-beta isoform expression profile to that of EA Cancers invasive through the esophageal wall had a higher percent of cells with cytoplasmic expression of ER-B1 than tumors limited to the wall (T3 vs. T1 and T2, p=0.051). We conclude that ER-B1, ER-B2, ER-B3 and ER-B5 are overexpressed in EA compared to its precursor lesion BMND, suggesting a significant biological role for steroid hormones in EA.