title: HER3 Expression Is a Marker of Tumor Progression in Premalignant Lesions of the Gastroesophageal Junction.
abstract: Overexpression of receptor tyrosine kinases (RTK), including members of the HER family, has prognostic and therapeutic significance in invasive esophagogastric carcinoma. RTK expression in premalignant gastroesophageal lesions has not been extensively explored. Formalin-fixed paraffin-embedded tissue samples of esophageal biopsy specimens from 73 patients with Barrett's esophagus with either low-grade dysplasia (LGD) (n = 32) or high-grade dysplasia (HGD) (n = 59) were analyzed for HER1, HER2, HER3 and CMET expression by immunohistochemistry (IHC). Immunophenotype was correlated with histologic and clinical features. High-grade dysplasia (HGD) was associated with overexpression of HER1 (20.7% vs. 3.1%, p = 0.023), HER2 (5.3% vs. 0.0%, p = 0.187) and HER3 (47.4% vs. 9.4%, p<0.001) compared to low-grade dysplasia (LGD). There was a significant association of HER2 (20.0% vs. 2.1%, p = 0.022) and HER3 (80.0% vs. 40.4%, p = 0.023) overexpression in HGD lesions associated with foci of invasive carcinoma compared to those without invasive foci. Overexpression of CMET was observed in 42.9% of specimens, was increasingly observed with HGD compared to LGD (58.3% vs. 36.7%, p = 0.200), and was most often co-expressed with HER3 (62.5% of HER3-positive specimens vs. 38.2% of HER3-negative specimens, p = 0.212). In summary, HER3 is frequently overexpressed in high-grade dysplastic lesions of the gastroesophageal junction and may be a marker of invasive progression. These data provide rationale for targeting HER2 and HER3 pathways in an early disease setting to prevent disease progression.
authors: Department of Surgery, University of Pennsylvania, Philadelphia, PA, United States of America.
authors: Brett L
authors: BL
authors: Ecker
authors: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
authors: Laura
authors: L
authors: Taylor
authors: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
authors: Paul J
authors: PJ
authors: Zhang
authors: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
authors: Emma E
authors: EE
authors: Furth
authors: Department of Gastroenterology, University of Pennsylvania, Philadelphia, PA, United States of America.
authors: Gregory G
authors: GG
authors: Ginsberg
authors: Department of Surgery, University of Pennsylvania, Philadelphia, PA, United States of America.
authors: Matthew T
authors: MT
authors: McMillan
authors: Department of Surgery, University of Pennsylvania, Philadelphia, PA, United States of America.
authors: Jashodeep
authors: J
authors: Datta
authors: Department of Surgery, University of Pennsylvania, Philadelphia, PA, United States of America.
authors: Brian J
authors: BJ
authors: Czerniecki
authors: Department of Surgery, University of Pennsylvania, Philadelphia, PA, United States of America.
authors: Robert E
authors: RE
authors: Roses
mesh_terms: D000368:Aged; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004943:Esophagogastric Junction / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; C508053:ERBB2 protein, human; C581292:ERBB3 protein, human