Universität zu Köln

Plum, Patrick Sven, Gebauer, Florian, Kraemer, Max, Alakus, Hakan, Berlth, Felix, Chon, Seung-Hun ORCID: 0000-0002-8923-6428, Schiffmann, Lars, Zander, Thomas, Buettner, Reinhard, Hoelscher, Arnulf Heinrich, Bruns, Christiane Josephine, Quaas, Alexander and Loeser, Heike (2019). HER2/neu (ERBB2) expression and gene amplification correlates with better survival in esophageal adenocarcinoma. BMC Cancer, 19. LONDON: BMC. ISSN 1471-2407

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Abstract

BackgroundHER2 (ERBB2 or HER2/neu) is a tyrosine-kinase increasing cell proliferation. Overexpression/amplification of HER2 is correlated with worse prognosis in solid malignancies. Consequently, HER2 targeting is established in breast and upper gastrointestinal tract cancer. There are conflicting data concerning the impact of HER2 overexpression on esophageal adenocarcinoma (EAC), as most studies do not differ between cancers of the esophagus/gastroesophageal junction and the stomach. The aim of this study was to analyze the expression/amplification of HER2 in EAC in correlation to clinicopathological data to verify its prognostic impact.MethodsWe analyzed 428 EAC patients that underwent transthoracic thoraco-abdominal esophagectomy between 1997 and 2014. We performed HER2 immunohistochemistry (IHC) according to the guidelines and fluorescence-in-situ-hybridization (FISH) for IHC score2+, using tissue micro arrays (TMA) with up to eight biopsies from the surface and infiltration area of a single tumor for evaluating HER2-heterogeneity and single-spot TMA. The HER2-status was correlated with clinicopathological data.ResultsHER2-positivity was found in up to 14.9% in our cohort (IHC score 3+ or IHC score 2+ with gene amplification) and demonstrated a significantly better overall survival (OS) in correlation to HER2-negative tumors (median OS 70.1 vs. 24.6months, p=0.006). HER2-overexpression was more frequently seen in lower tumor stages (pT1/pT2, p=0.038), in the absence of lymphatic metastases (pN0/pN+, p=0.020), and was significantly associated with better histological grading (G1/G2) (p=0.041).ConclusionWe demonstrated a positive prognostic impact of HER2 overexpression in a large cohort of EAC, contrary to other solid malignancies including gastric cancer and breast cancer, but consistent to the results of a large study on EAC from 2012.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Plum, Patrick Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Gebauer, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Kraemer, Max UNSPECIFIED UNSPECIFIED UNSPECIFIED Alakus, Hakan UNSPECIFIED UNSPECIFIED UNSPECIFIED Berlth, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Chon, Seung-Hun UNSPECIFIED orcid.org/0000-0002-8923-6428 UNSPECIFIED Schiffmann, Lars UNSPECIFIED UNSPECIFIED UNSPECIFIED Zander, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoelscher, Arnulf Heinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruns, Christiane Josephine UNSPECIFIED UNSPECIFIED UNSPECIFIED Quaas, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Loeser, Heike UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-159425
DOI:	10.1186/s12885-018-5242-4
Journal or Publication Title:	BMC Cancer
Volume:	19
Date:	2019
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1471-2407
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GASTROESOPHAGEAL JUNCTION; AMERICAN-PATHOLOGISTS; BREAST-CANCER; PROGNOSIS; CHEMORADIATION; HETEROGENEITY; TRASTUZUMAB; GUIDELINE; BIOPSIES; SOCIETY Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15942