title: Intratumoral heterogeneity of HER2 protein and amplification of HER2 gene in salivary duct carcinoma.
abstract: Salivary duct carcinoma (SDC) is an aggressive adenocarcinoma of the salivary glands, and accounts for 1-3% of all malignant salivary gland tumors, resembling morphologically invasive ductal carcinoma (IDC) of the breast. In contrast to IDC of the breast and gastric carcinoma (GC), the study of human epidermal growth factor receptor 2 (HER2) in SDC has not progressed. Therefore, we investigated the relationship between HER2 protein expression and amplification of the HER2 gene, and compared them in terms of intratumoral heterogeneity (ITH) in 13 cases of SDC using immunohistochemistry and dual color in situ hybridization. We found seven cases with protein overexpression (53.8%) and five cases with gene amplification (38.5%) in accordance with ASCO/CAP guidelines. ITH of HER2 protein expression was seen in seven cases (53.8%). Interestingly, the ratio of the HER2 gene showed homogenous distribution with or without the presence of ITH of HER2 protein expression. SDC tends to have more ITH of HER2 protein similarly to GC, in contrast to IDC of the breast. ITH of HER2 protein in SDC has no heterogeneity of the HER2 gene amplification. The mechanism of HER2 protein expression in SDC might proceed through a more complex pathway relative to that of IDC of the breast.
authors.affiliation: Department of Pathology, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kondo
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Joaquim Carreras
authors.initials: JC
authors.lastname: Esteban
authors.forename: Nobue
authors.initials: N
authors.lastname: Kumaki
authors.forename: Go
authors.initials: G
authors.lastname: Ogura
authors.forename: Chie
authors.initials: C
authors.lastname: Inomoto
authors.forename: Kenichi
authors.initials: K
authors.lastname: Hirabayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kajiwara
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sakai
authors.forename: Ryousuke
authors.initials: R
authors.lastname: Sugimoto
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Otsuru
authors.forename: Kenji
authors.initials: K
authors.lastname: Okami
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tsukinoki
authors.forename: Naoya
authors.initials: N
authors.lastname: Nakamura
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D018740:Genetic Heterogeneity; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D012468:Salivary Gland Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: heterogeneity; human epidermal growth factor receptor 2 (HER2); salivary duct carcinoma (SDC)