Immunohistochemical evaluation of a panel of tumor cell markers during malignant progression in Barrett esophagus.
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 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 beta-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.
van Dekken
Herman
H
Department of Pathology, Sint Franciscus Gasthuis, Rotterdam, the Netherlands.
Hop
Wim C J
WC
Tilanus
Hugo W
HW
Haringsma
Jelle
J
van der Valk
Hans
H
Wink
Josiane C
JC
Vissers
Kees J
KJ
D000230:Adenocarcinoma / Q000209:etiology / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000175:diagnosis / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D056741:Cyclin D; D016213:Cyclins / Q000096:biosynthesis; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000209:etiology / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D051176:beta Catenin / Q000096:biosynthesis
D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D056741:Cyclin D; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin