Immunohistochemical Evaluation of a Panel of Tumor Cell Markers During Malignant Progression in Barrett Esophagus

H (Herman) van Dekken, Hop, Hugo Tilanus, J Haringsma, H (Hans) van der Valk, JC Wink, K Vissers

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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 (beta-catenin), and TP53 (p53), in histologic sections of endoscopic biopsies of 86 patients with BE in various stages of neoplastic progression. The markers, except SAMD4, 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 P-catenin separated LGD from metaplasia, whereas protein overexpression of cyclin D1 and p53 discriminated HGD from LGD (all P <. 001). beta-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.
Original languageUndefined/Unknown
Pages (from-to)745-753
Number of pages9
JournalAmerican Journal of Clinical Pathology
Issue number5
Publication statusPublished - 2008

Research programs

  • EMC MM-03-24-01
  • EMC MM-03-47-02-A
  • EMC MM-03-47-06-A
  • EMC MM-03-47-11
  • EMC MM-04-20-01
  • EMC NIHES-01-66-01

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