Histopathologic grading of dysplasia in Barrett esophagus (BE) shows substantial interobserver and intraobserver variation. We used immunohistochemical analysis with a set of tumor cell markers, ie, epidermal growth factor receptor (EGFR), ERBB2 (HER2/neu), MYC, CDKN2A (p16), SMAD4, MET, CCND1 (cyclin D1), CTNNB1 (β-catenin), and TP53 (p53), in histologic sections of endoscopic biopsies of 86 patients with BE in various stages of neoplastic progression. The markers, except SMAD4, were scored as 0 (<1% of cells stained), 1 (1%-25%), 2 (26%-50%), or 3 (>50%). All markers, except EGFR, showed a significant trend for immunohistochemical protein overexpression during malignant progression in BE (P < .01). When the successive stages along the metaplasia-low-grade dysplasia (LGD)-high-grade dysplasia (HGD)-adenocarcinoma axis were compared, protein overexpression of β-catenin separated LGD from metaplasia, whereas protein overexpression of cyclin D1 and p53 discriminated HGD from LGD (all P < .001). β-Catenin can be helpful for a diagnosis of LGD in BE, although it stains positively in a subset only, whereas p53 remains an appropriate marker to define HGD. In case of doubt, cyclin D1 can be added to separate LGD from HGD in BE.

Adenocarcinoma, Barrett esophagus, Biomarker, Dysplasia, Immunohistochemistry
dx.doi.org/10.1309/AJCPO31THGVEUIDH, hdl.handle.net/1765/29191
American Journal of Clinical Pathology
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Erasmus MC: University Medical Center Rotterdam

van Dekken, H, Hop, W.C.J, Tilanus, H.W, Haringsma, J, van der Valk, H, Wink, J.C, & Vissers, K.J. (2008). Immunohistochemical evaluation of a panel of tumor cell markers during malignant progression in Barrett esophagus. American Journal of Clinical Pathology, 130(5), 745–753. doi:10.1309/AJCPO31THGVEUIDH