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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：

PURPOSE: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.

journal_name

J Cancer Res Clin Oncol

journal_title

Journal of cancer research and clinical oncology

authors

Lee MJ,Kim N,Choung HK,Choe JY,Khwarg SI,Kim JE

doi

10.1007/s00432-015-2009-z

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

125-33

issue

eissn

0171-5216

issn

1432-1335

pii

10.1007/s00432-015-2009-z

journal_volume

142

pub_type

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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.