Goblet Cells Are Depleted with Advancing Degrees of Preneoplasia in Barrett's Esophagus
Agoston T Agoston, Anapat Sanpavat, Robert D Odze, Amitabh Srivastava. Brigham & Women's Hospital, Boston, MA
Background: A previous study by our group showed that the proportion of goblet cells in index biopsies of patients with Barrett's Esophagus (BE) is inversely proportional to the risk of malignancy, and this led to the hypothesis that goblet cells may represent a successful adaptive form of metaplasia that protects the mucosa from the carcinogenic effects of reflux. However, the topographic distribution of goblet cells in relationship to neoplasia is unknown, and no prior studies have evaluated resection specimens where anatomic distribution can be more accurately noted. The aim of this study was to evaluate the goblet cell density in adjacent non-neoplastic BE both adjacent to, near, and distant from areas of neoplasia in BE patients who had a resection for dysplasia or carcinoma without neoadjuvant therapy.
Design: Routinely processed resection specimens from 40 patients who had a distal esophagogastrectomy for high-grade dysplasia (N=1) or adenocarcinoma (N=39) were evaluated histologically for the mean number of goblet cells per crypt (GC/crypt) in areas adjacent to (<10 crypts), near (10-20 crypts) and distant from (>20 crypts) areas of neoplasia. Goblet cell counts were compared between different mucosal locations in proximity to neoplasia in all cases, and then also compared between areas of low vs. high-grade dysplasia.
Results: Overall, there was a significant decrease in goblet cell counts in areas of mucosa adjacent to neoplasia (mean GC/crypt = 3.8) vs. near (5.2) or distant from (5.5) neoplasia, (p=0.029). In all mucosal locations, there was a highly significant decrease in goblet cell counts in areas of high vs. low-grade dysplasia. For instance, mucosa adjacent to neoplasia showed a crypt count of 3.9 vs. 1.5 (p=0.05) for low vs. high grade dysplasia, respectively, values of 5.4 vs. 1.5 (p=0.005) for mucosa near low vs. high grade dysplasia, respectively, and values of 6.0 vs. 1.2 (p<0.001) for mucosa distant from low vs. high grade dysplasia, respectively. Goblet cell density did not change significantly with distance from invasive carcinoma.
Conclusions: In BE, goblet cells are depleted within the mucosal field in which neoplasia develops. Further studies are needed to determine whether goblet cell depleted mucosa is at increased risk for neoplasia, or neoplasia itself induces a shift in the columnar metaplasia that occurs in the background mucosa, perhaps due to changes in cell differentiation. Retention of goblet cells in areas adjacent to cancer was likely due to the destructive effects of cancer on the surrounding neoplastic precursor mucosa.
Monday, March 19, 2012 1:00 PM
Poster Session II # 82, Monday Afternoon