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.

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Keywords Adenocarcinoma, Barrett esophagus, Biomarker, Dysplasia, Immunohistochemistry
Persistent URL dx.doi.org/10.1309/AJCPO31THGVEUIDH, hdl.handle.net/1765/29191
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Citation
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