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.
Department of Pathology, Sint Franciscus Gasthuis, Rotterdam, the Netherlands.
Herman
H
van Dekken
Wim C J
WC
Hop
Hugo W
HW
Tilanus
Jelle
J
Haringsma
Hans
H
van der Valk
Josiane C
JC
Wink
Kees J
KJ
Vissers
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