title: Increased gene copy number of HER2 and concordant protein overexpression found in a subset of eyelid sebaceous gland carcinoma indicate HER2 as a potential therapeutic target.
abstract: OBJECTIVE
  To identify crucial molecular alterations of receptor tyrosine kinases that can be used as potential therapeutic targets for eyelid sebaceous gland carcinoma (SbGC).
  
  
  METHODS
  The expression levels of HER2, EGFR, C-MET, and FGFR1 were determined by immunohistochemistry (IHC). The copy numbers of the HER2, EGFR, C-MET, and FGFR1 genes were assessed by fluorescence in situ hybridization. The IHC and molecular results were correlated with the clinical parameters.
  
  
  RESULTS
  A total of 49 patients with eyelid SbGC were included in this study. HER2, EGFR, C-MET, and FGFR1 protein expression was detected in 8 of 44 (16.3 %), 8 of 45 (17.8 %), 3 of 35 (8.6 %), and 0 of 45 patient samples, respectively. Increased copy numbers of the HER2 gene were found in 5 of 42 patient samples (11.9 %), including two with amplification (4.7 %) and three with polysomy (7.2 %). EGFR amplification was found in 2 of 33 (6.1 %) and FGFR1 amplification in 4 of 33 patient samples (12.1 %; high-level amplification in one and low-level amplification in three). None of the samples examined exhibited C-MET amplification. Gene copy number of the HER2 gene was correlated with its protein expression (p < 0.0001), whereas copy number of EGFR, C-MET, or FGFR1 was not correlated with protein expression. However, samples with EGFR amplification also exhibited a high level of expression of this protein.
  
  
  CONCLUSIONS
  Extra copies of the HER2, EGFR, and FGFR1 genes were identified in a 6-12 % of eyelid SbGCs. A high level of concordant HER2 expression detected by immunohistochemistry can be predictive of a copy number gain of the HER2 gene. Our data suggest that the therapeutic targeting of HER2 might benefit for a subset of patients with periocular SbGCs.
authors.affiliation: Department of Ophthalmology, Hallym University Sacred Hospital, Anyang, Korea.
authors.forename: Min Joung
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Namju
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Seoul Municipal Government-Seoul National University Boramae Hospital, Seoul, Korea.
authors.forename: Ho-Kyung
authors.initials: HK
authors.lastname: Choung
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seoul, Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Choe
authors.affiliation: Department of Ophthalmology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Sang In
authors.initials: SI
authors.lastname: Khwarg
authors.affiliation: Department of Pathology, Seoul Municipal Government-Seoul National University Boramae Hospital, #20 Boramae-ro 5-gil, Dongjak-Gu, Seoul, 156-707, Korea. npol181@snu.ac.kr.
authors.forename: Ji Eun
authors.identifier: http://orcid.org/0000-0002-2156-9875
authors.initials: JE
authors.lastname: Kim
mesh_terms: D018266:Adenocarcinoma, Sebaceous / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005142:Eyelid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D018628:Gene Dosage / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism*; D012626:Sebaceous Gland Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met; D018719:Erb-b2 Receptor Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C496348:FGFR1 protein, human
keywords: C-MET; EGFR; Eyelid; FGFR1; HER2; Sebaceous gland carcinoma