Universität zu Köln

Christgen, Matthias, Bartels, Stephan ORCID: 0000-0002-8903-2345, Radner, Martin, Raap, Mieke, Rieger, Luisa, Christgen, Henriette, Gluz, Oleg, Nitz, Ulrike, Harbeck, Nadia, Lehmann, Ulrich and Kreipe, Hans (2019). ERBB2 mutation frequency in lobular breast cancer with pleomorphic histology or high-risk characteristics by molecular expression profiling. Gene Chromosomes Cancer, 58 (3). S. 175 - 186. HOBOKEN: WILEY. ISSN 1098-2264

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Abstract

HER2-positive breast cancer is defined by amplification or overexpression of the HER2/ERBB2 oncogene and accounts for about 15% of breast cancer cases. Somatic mutation of ERBB2 is an alternative mechanism, by which activation of HER2 signaling can occur. ERBB2 mutation has been associated with invasive lobular breast cancer (ILBC). This study investigates the frequency and phenotype of ILBC harboring mutated ERBB2. The ERBB2 mutation status was determined by next generation sequencing and/or pyrosequencing in n = 106 ILBCs, including n = 86 primary or locally recurrent tumors and n = 20 metastases from visceral organs, soft tissue, or skin. Immunohistochemical characteristics were determined using tissue microarrays. This series was enriched for ILBCs with pleomorphic histology and/or high-risk expression profiles (Oncotype DX, recurrence score RS > 25). Nearly all specimens were E-cadherin-negative (99%), estrogen receptor (ER)-positive (92%), and lacked ERBB2 overexpression (96%). ERBB2 mutations (p.V777L, p.L755S, p.S310F) were identified in 5/106 (5%) cases. ERBB2-mutated cases included 2/86 (2%) primary tumors and 3/20 (15%) metastases (P = 0.045). ERBB2-mutated cases were associated with loss of ER (2/7, 29%, P = 0.035) and histological grade 3 (4/34, 12%, P = 0.023), but not with solid growth (3/31, 10%, P = 0.148) or pleomorphic histology (2/27, 7%, P = 0.599). No ERBB2 mutation was detected in ILBCs with RS > 25 (0/22, 0%). In 10 patients with multiple matched specimens (n = 25), the ERBB2 mutational status was always concordant. In summary, a small subset of ILBCs harbors potentially actionable ERBB2 mutations. In ERBB2-mutated ILBCs, no association with pleomorphic histology was found.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Christgen, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Bartels, Stephan UNSPECIFIED orcid.org/0000-0002-8903-2345 UNSPECIFIED Radner, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Raap, Mieke UNSPECIFIED UNSPECIFIED UNSPECIFIED Rieger, Luisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Christgen, Henriette UNSPECIFIED UNSPECIFIED UNSPECIFIED Gluz, Oleg UNSPECIFIED UNSPECIFIED UNSPECIFIED Nitz, Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Harbeck, Nadia UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehmann, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Kreipe, Hans UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-156177
DOI:	10.1002/gcc.22716
Journal or Publication Title:	Gene Chromosomes Cancer
Volume:	58
Number:	3
Page Range:	S. 175 - 186
Date:	2019
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1098-2264
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CARCINOMA IN-SITU; PIK3CA MUTATIONS; HER2 MUTATIONS; AMPLIFICATION; PORTRAITS; NERATINIB Multiple languages Oncology; Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15617