HER‐2/neu gene amplification in relation to expression of HER2 and HER3 proteins in patients with esophageal adenocarcinoma. Issue 3 (21st October 2013)

• Record Type: Journal Article
• Authors: Yoon, Harry H.; Sukov, William R.; Shi, Qian; Sattler, Christopher A.; Wiktor, Anne E.; Diasio, Robert B.; Wu, Tsung‐Teh; Jenkins, Robert B.; Sinicrope, Frank A.
• Is Part Of: Cancer. Volume 120:Issue 3(2014)
• Page Start: 415
• Page End: 424
• Publication Date: 2013-10-21
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.28435
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="cncr28435-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>Human epidermal growth factor receptor 2 (HER2) is a therapeutic target in patients with esophageal adenocarcinoma (EAC), with gene amplification used as a selection criterion for treatment, although to the authors' knowledge the concordance between amplification and HER2 protein expression remains undefined in EAC. Furthermore, the association between HER2 and its interacting partner, human epidermal growth factor receptor 3 (HER3), is unknown yet appears to be of potential therapeutic relevance.</p> </sec> <sec id="cncr28435-sec-0002" sec-type="section"> <title>METHODS</title> <p>Patients with untreated EACs (N = 673) were analyzed for <italic>HER2</italic> amplification and polysomy 17 by fluorescence in situ hybridization in parallel with immunohistochemistry (IHC) (IHC scores of 0‐1+, 2+, and 3+). Amplification was defined as <italic>HER2</italic>/<italic>CEP17</italic> ≥ 2. HER3 expression by IHC was analyzed in randomly selected cases (n = 224). IHC and fluorescence in situ hybridization results were compared using least squares linear regression.</p> </sec> <sec id="cncr28435-sec-0003" sec-type="section"> <title>RESULTS</title> <p>Overall, 17% of the EACs (116 of 673 EACs) were <italic>HER2</italic>‐amplified with an amplification frequency that was highest among IHC3+ cases (89%) and declined among IHC2+ cases (13%) and IHC0 to IHC1+ cases (4%). Among <italic>HER2</italic>‐amplified cases, the level of amplification increased linearly with HER2 membranous expression (<italic>HER2</italic>/<italic>CEP17</italic> ratio: 7.9 in IHC3+ and 5.5 in IHC2+ vs 2.8 in IHC0 to IHC1+ [<italic>P</italic> < .0001]), with 14% of amplified tumors demonstrating absent/faint expression (IHC0 to IHC1+). Polysomy 17 was not found to be associated with HER2 expression. Cytoplasmic HER3 expression was detected in 87% of tumors (195 of 224 tumors) and was found to be significantly associated with better differentiation (<italic>P</italic> < .0001). Stepwise increases in HER3 expression were associated with higher HER2 expression levels (<italic>P</italic> = .0019).</p> </sec> <sec id="cncr28435-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>Levels of HER2 protein expression and amplification were found to be linearly associated and highly concordant. Among amplified tumors with absent/faint expression, the level of amplification was low. Frequent expression of HER3 suggests its relevance as a therapeutic target, and its significant association with HER2 supports ongoing efforts to inhibit HER2/HER3 in patients with EAC. <bold><italic>Cancer</italic> 2014;120:415–424</bold>. © <italic>2013 American Cancer Society</italic>.</p> </sec> </abstract>