title: Overexpression and gene amplification of both ERBB2 and EGFR in an esophageal squamous cell carcinoma revealed by fluorescence in situ hybridization, multiplex ligation-dependent probe amplification and immunohistochemistry.
abstract: EGFR and ERBB2 belong to the EGFR gene family. In esophageal squamous cell carcinomas (SCCs), amplification of EGFR or ERBB2 is usually mutually exclusive. EGFR amplification occurs in approximately 15% of SCCs, ERBB2 occurs in less than 5%. Here, we report the co-amplification of EGFR and ERBB2 in an ulcerative and infiltrating-type SCC that measured approximately 4.2 × 2.7 × 1.2 cm with a superficial lesion occurring in the thoracic esophagus of a 72-year-old man. Multiplex ligation-dependent probe amplification using representative tumor sections showed gain of CCND1 and coincident amplification of ERBB2 or EGFR or neither. Immunohistochemistry and fluorescence in situ hybridization revealed that the tumor comprised three cancer-cell populations: well-differentiated SCC with high-level ERBB2 amplification and ERBB2 overexpression, more infiltrative poorly-differentiated SCC with high-level EGFR amplification and EGFR overexpression, and poorly-differentiated SCC lacking any ERBB2 or EGFR abnormality. These three populations each had low-level CCND1 amplification and nuclear cyclin D1 overexpression. This histological topology and gene amplification combinations suggested that genetic instability first produced CCND1 amplification, and then ERBB2 or EGFR gene amplification occurred. It is further speculated that during cancer progression and clonal selection indecisive predominance of either clone caused the rare co-amplification of ERBB2 and EGFR in a single chimeric tumor.
authors: Department of Molecular and Cellular Pathology, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan.
authors: Takeru
authors: T
authors: Oyama
authors: Department of Gastroenterologic Surgery, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan.
authors: Koichi
authors: K
authors: Okamoto
authors: Department of Molecular and Cellular Pathology, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan.
authors: Ritsuko
authors: R
authors: Nakamura
authors: Department of Molecular and Cellular Pathology, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan.
authors: Ryosuke
authors: R
authors: Tajiri
authors: Pathology Section, University Hospital, Kanazawa University, Ishikawa, Japan.
authors: Hiroko
authors: H
authors: Ikeda
authors: Department of Gastroenterologic Surgery, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan.
authors: Itasu
authors: I
authors: Ninomiya
authors: Department of Molecular and Cellular Pathology, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan.|Pathology Section, University Hospital, Kanazawa University, Ishikawa, Japan.
authors: Akishi
authors: A
authors: Ooi
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000378:metabolism*; D000077277:Esophageal Squamous Cell Carcinoma; D005784:Gene Amplification / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008297:Male; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human; C508053:ERBB2 protein, human
keywords: CCND1; EGFR; ERBB2; FISH; MLPA; esophageal cancer; gene amplification