title: Her-2 Expression in Gastroesophageal Intestinal Metaplasia, Dysplasia, and Adenocarcinoma.
abstract: Overexpression of human epidermal growth factor receptor 2 protein (Her-2) in Barrett neoplasia is significant for targeted therapy with trastuzumab. Here, we studied the frequency of Her-2 overexpression in Barrett adenocarcinoma and precursor lesions. Retrospective formalin-fixed paraffin-embedded tissue samples of 25 normal (NM) esophageal mucosa, 50 Barrett esophagus (BE) without dysplasia, 49 BE with low-grade dysplasia (LGD), 50 BE with high-grade dysplasia (HGD), and 50 invasive adenocarcinoma (ICA) were used. A BE tissue microarray was built and analyzed by Her-2 immunohistochemistry (IHC) and Her-2 dual in situ hybridization (DISH). Her-2 IHC expression was negative in NM and low in 26% of BE (IHC score: 1+) and in 24.5% of LGD (IHC score: 1 to 2+). Her-2 overexpression was seen in 28% of HGD and in 24% of ICA (IHC score: 2 to 3+). Her-2 DISH was negative in NM and BE but positive in 6% of LGD, 20% of HGD, and 18% of ICA. Differences in Her-2 DISH positivity between NM and HGD or ICA were statistically significant (P=0.02), but those between NM and LGD or HGD and ICA were not (P=0.2). Although Her-2 overexpression results in ICA were similar to previous reports, the finding of 28% in HGD was unexpected and may have clinical implications. Positive Her-2 DISH in 6% of LGD is novel, suggesting a role of Her-2 during BE progression.
authors.affiliation: Departments of *Gastrointestinal Oncology †Anatomic Pathology ∥Chemical Biology and Molecular Medicine ¶Tumor Biology, H. Lee Moffitt Cancer Center, Research Institute Departments of §Pathology and Cell Biology ‡Oncological Sciences, University of South Florida, Tampa, FL.
authors.forename: Khaldoun
authors.initials: K
authors.lastname: Almhanna
authors.forename: Marilin
authors.initials: M
authors.lastname: Rosa
authors.forename: Evita
authors.initials: E
authors.lastname: Henderson-Jackson
authors.forename: Kun
authors.initials: K
authors.lastname: Jiang
authors.forename: Rania
authors.initials: R
authors.lastname: Shamekh
authors.forename: Zena
authors.initials: Z
authors.lastname: Sayegh
authors.forename: Mokenge P
authors.initials: MP
authors.lastname: Malafa
authors.forename: Domenico
authors.initials: D
authors.lastname: Coppola
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human