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her2 equivocal

Luisa Vera Muscatello, Enrico Di Oto, Giuseppe Sarli, Valentina Monti, Maria Pia Foschini, Cinzia Benazzi, Barbara Brunetti
Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase receptor overexpressed in a subset of breast cancer due to HER2 gene amplification. HER2 protein is expressed in feline mammary carcinomas, but little is known about its cytogenetic alterations. The aim of this study was to evaluate HER2 gene amplification status and its correlation with HER2 protein expression in feline mammary carcinomas. Feline mammary carcinomas were retrospectively selected and immunohistochemically (IHC) evaluated for HER2 protein expression...
November 1, 2018: Veterinary Pathology
Beth Z Clark, Agnieszka Onisko, Binara Assylbekova, Xin Li, Rohit Bhargava, David J Dabbs
Biomarker analysis of invasive breast carcinoma is useful for prognosis, as surrogate for molecular subtypes of breast cancer, and prediction of response to adjuvant and neoadjuvant systemic therapies. Breast cancer intratumoral heterogeneity is incompletely studied. Comprehensive biomarker analysis of estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67 labeling index was performed on each tissue block of 100 entirely submitted breast tumors in 99 patients. Invasive carcinoma and in situ carcinoma was scored using semiquantitative histologic score (H-score) for ER and PR, HER2 expression from 0 to 3+, and percentage positive cells for Ki67...
October 16, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Anchalee Tantiwetrueangdet, Ravat Panvichian, Sansanee Wongwaisayawan, Natthaporn Sueangoen, Panuwat Lertsithichai
Breast cancers with amplification and overexpression of human epithelial growth factor receptor 2 (HER2) are associated with poor prognosis, and targeted for anti-HER2 therapy. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are currently the recommended methods to asses HER2 overexpression/amplification. Droplet digital PCR (ddPCR), a highly accurate method to quantify DNA copy number, is potentially a robust alternative for HER2 diagnostics. In the FISH assay and most of previous ddPCR reports, chromosome 17 centromere (CEP17) has been used as the reference control to determine HER2/CEP17 ratio...
October 3, 2018: Medical Oncology
Cameron Neely, Shuo You, Pia M Mendoza, Ritu Aneja, Aysegul A Sahin, Xiaoxian Li
INTRODUCTION: Oncotype DX (ODX) testing uses reverse transcription polymerase chain reaction (RT-PCR) to predict distant recurrence rate of estrogen receptor positive (ER+)/HER2-negative (HER2-)/lymph node-negative (LN-) breast cancers. ODX also reports the status of breast cancer biomarkers, ER, progesterone receptor (PR), and HER2. This study examined the discrepancy rate of breast cancer biomarker status as reported by ODX vs routinely used immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) methods...
September 19, 2018: Breast Journal
Tülay Canda, Ekrem Yavuz, Necmettin Özdemir, Sennur İlvan, Serpil Sak Dizbay, Merih Güray Durak, Sıtkı Tuzlalı, Osman Zekioğlu, Atakan Demir, Handan Onur, Kasım Üstündağ, Burçe Göktaş
Objective: As patients with increased human epidermal growth factor receptor (HER2) overexpression are more likely to benefit from trastuzumab treatment, the accuracy of HER2 receptor status in breast cancer patients is significant for appropriate disease management. However, this assessment is not harmonized and results may be highly variable between centers. The aim of this study was to investigate the degree of interlaboratory variability in the results of HER2 expression reported by 5 participating centers and to assess the concordance between these centers and a reference laboratory...
July 2018: European Journal of Breast Health
Somaye Y Zare, Leo Lin, Abrar G Alghamdi, Svenja Daehne, Andres A Roma, Farnaz Hasteh, Marie Dell'Aquila, Oluwole Fadare
The 2013 American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) guidelines classified breast cancers with a florescence in situ hybridization (FISH) dual probe HER2/CEP17 ratio ≥ 2 as "amplified", inclusive of cases with a HER2 copy number< 4. The 2018 ASCO/CAP update assigns HER2/neu status for the latter group in a fashion that is highly dependent on the associated immunohistochemical findings. Herein, the authors define the frequency, immunohistochemical correlates, and other clinicopathologic features of breast cancers with HER2/CEP17 ratio ≥ 2 and HER2/neu copy number< 4 (group-A), based on an analysis of an institutional cohort assessed for HER2/neu status by both FISH and immunohistochemistry and scored using 2013 ASCO/CAP criteria...
August 16, 2018: Human Pathology
Gyula Pekar, Ioanna Kasselaki, Agnes P Lukacs, Csaba Dekany, Dan Hellberg, Tibor Tot
AIMS: Genetic heterogeneity can pose a challenge to identifying eligible cases for targeted therapy in the human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) 2+ breast carcinoma group. In this study, we characterized this subset of tumors according to clinicopathological parameters. METHODS AND RESULTS: We assessed 1000 tumor cells per case and recorded the number of HER2 and chromosome enumeration probe 17 (CEP17) copies using gene-protein assay slides...
August 16, 2018: Histopathology
Parth S Shah, Shiva Murarka, Anupam Joshi, Bhavna Mehta, Vipal Parmar, Nidhi Shah, Khushbu Patel, Jacob Sands
Introduction: Human epidermal growth factor receptor 2 (HER2) amplification is present in almost 15%-20% of breast cancer tumors, making it an important parameter for testing. The present study was designed to evaluate a chip-based digital PCR (dPCR) system for assessing HER2 amplification from formalin-fixed paraffin-embedded breast carcinoma tissue and to compare this system with immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Materials and methods: A total of 84 breast carcinoma tissue samples were analyzed by IHC, FISH, and chip-based dPCR in a blinded manner...
2018: Breast Cancer: Targets and Therapy
Frederike Bensch, A H Brouwers, M N Lub-de Hooge, J R de Jong, B van der Vegt, S Sleijfer, E G E de Vries, C P Schröder
BACKGROUND: Up-to-date information on human epidermal growth factor receptor 2 (HER2) status in breast cancer (BC) is important, as expression can vary during the course of the disease, necessitating anti-HER2 therapy adjustments. Repeat biopsies, however, are not always possible. In this feasibility trial we assessed whether 89 Zr-trastuzumab PET could support diagnostic understanding and aid clinical decision making, when HER2 status could not be determined by standard work up. Additionally, HER2 status on circulating tumour cells (CTCs) was assessed...
December 2018: European Journal of Nuclear Medicine and Molecular Imaging
Libo Yang, Zhang Zhang, Jiayuan Li, Min Chen, Jieliang Yang, Jing Fu, Hong Bu, Shaoxian Tang, Yueping Liu, Huixiang Li, Xiaomei Li, Fangping Xu, Xiaodong Teng, Yinghong Yang, Yun Ma, Shuangping Guo, Jinfen Wang, Deyu Guo
Objective: To investigate the proportion of HER2 gene amplifications and the association between the HER2-IHC-staining pattern and gene status in IHC-2+ breast cancers according to 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. Methods: We retrospectively analyzed and re-evaluated the IHC-staining pattern of 2538 IHC-2+ surgical specimens of breast cancer from November 2014 to October 2015 in 12 institutions. All cases used for building a prediction model of HER2 gene amplification according to the IHC-staining pattern and were randomly divided into a training set (n = 1914) or validation set (n = 624)...
2018: Journal of Cancer
Neelam V Desai, Vanda Torous, Joel Parker, James T Auman, Gary B Rosson, Cassandra Cruz, Charles M Perou, Stuart J Schnitt, Nadine Tung
The 2013 update of the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) human epidermal growth factor receptor 2 (HER2) testing guidelines recommend using an alternative chromosome 17 probe assay to resolve HER2 results determined to be equivocal by immunohistochemistry (IHC) or fluorescence in-situ hybridization (FISH). However, it is unclear if cases considered HER2-positive (HER2+ ) by the alternative probe method are similar to those classified as HER2+ by traditional IHC and FISH criteria and benefit the same from HER2-targeted therapies...
July 11, 2018: Breast Cancer Research: BCR
S F Wu, Y Y Liu, X D Liu, Y Jiang, Y F Luo, Q C Cui, Z Y Liang, X Zeng
Objective: To investigate human epidermal growth factor 2 (HER2) gene status and in situ mRNA expression in breast cancers with immunohistochemistry(IHC) 1+ , and to reveal HER2 positive rate in these patients to provide reference data for obtaining precise HER2 results and modifying relevant clinical strategy to breast cancer. Methods: Sixty-five IHC 1+ formalin-fixed and paraffin-embedded samples of invasive breast carcinoma of no special type (IBC-NST) were collected by surgical operation at Peking Union Medical College Hospital during 2011 to 2013...
July 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Ayano Nakamura, Ken Yamaguchi, Sachiko Minamiguchi, Ryusuke Murakami, Kaoru Abiko, Junzo Hamanishi, Eiji Kondoh, Tsukasa Baba, Masaki Mandai, Noriomi Matsumura
Mucinous adenocarcinoma, gastric type (GAS) is difficult to diagnose and shows poor prognosis. Trastuzumab, an anti-human epidermal growth factor type 2 (HER2) monoclonal antibody, is effective in HER2-positive stomach cancer. The objectives of this study were to identify the clinicopathological characteristics of GAS and to evaluate HER2 expression in GAS. We retrospectively reviewed 322 cervical cancer cases diagnosed at the Kyoto University Hospital from 2010 to 2016. The incidence, clinical factors including age, stage, and lymph node status, tumor markers, immunoreactive expression of MUC6, HIK1083, and HER2, and HER2 amplification were evaluated...
July 10, 2018: Medical Molecular Morphology
Caterina Marchiò, Patrizia Dell'Orto, Laura Annaratone, Felipe C Geyer, Tiziana Venesio, Enrico Berrino, Ludovica Verdun di Cantogno, Andrea Garofoli, Nelson Rangel, Laura Casorzo, Carmine dell'Aglio, Patrizia Gugliotta, Elena Trisolini, Alessandra Beano, Francesca Pietribiasi, Renzo Orlassino, Paola Cassoni, Achille Pich, Filippo Montemurro, Marcella Mottolese, Anne Vincent-Salomon, Frédérique Penault-Llorca, Enzo Medico, Charlotte K Y Ng, Giuseppe Viale, Anna Sapino
The American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2013 guidelines for HER2 assessment have increased the number of HER2 equivocal breast carcinomas following in situ hybridization reflex testing, that is, HER2 "double equivocal" (equivocal protein expression and equivocal gene copy number). Forty-five double-equivocal carcinomas were subjected to Prosigna analysis. Twenty-seven cases were investigated for the expression of genes found to be differentially expressed between estrogen receptor (ER)-positive/HER2-positive (N=22) and ER-positive/HER2-negative (N=22) control cases...
September 2018: American Journal of Surgical Pathology
Somaye Zare, Leo Lin, Abrar G Alghamdi, Svenja Daehne, Andres A Roma, Farnaz Hasteh, Marie Dell'Aquila, Oluwole Fadare
At our institution, breast cancer cases that generate an equivocal HER2/neu (HER2) result by fluorescence in situ hybridization (FISH) using the dual HER2/chromosome enumeration probe (CEP17) are reflexed to an assay that utilizes an alternative control probe (lissencephaly gene1 [LIS1] [17p13.3]/retinoic acid receptor α [RARA] [17q21.2]). This study examines whether cancers that are classified as HER2-amplified with an alternate probe are clinicopathologically similar to those that are classified as such using the HER2/CEP17 probe...
September 2018: American Journal of Surgical Pathology
Asmanaz Saleem Nadaf, Hephzibah Rani, Udipi Shastri Dinesh
Background and Objectives: Gastric cancer is the fourth most common cancer worldwide and ranks fifth in India. Surgical resection is curative in early stage gastric cancers. Most of the gastric cancers are diagnosed at an advanced stage necessitating multimodality treatment strategies. Based on the ToGA trial, the international regulatory agencies have recently approved trastuzumab in locally advanced and metastatic gastric and gastroesophageal adenocarcinomas expressing HER2. Since there are limited studies from India and no published data available from this part of North Karnataka, we undertook this study to evaluate the frequency of expression of HER2 in gastric and gastroesophageal adenocarcinomas and to correlate it with various clinicopathological variables...
May 26, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
Ikuko Hirai, Keiji Tanese, Yoshio Nakamura, Atsushi Otsuka, Yasuhiro Fujisawa, Yuki Yamamoto, Hiroo Hata, Taku Fujimura, Shigeto Matsushita, Koji Yoshino, Kaori Kameyama, Masayuki Amagai, Takeru Funakoshi
The human epidermal growth factor receptor 2 (HER2) is recognized as an oncogene as well as a therapeutic target in various cancers. Certain patients with advanced extramammary Paget's disease (EMPD) have also been reported to express HER2, which is therefore considered a therapeutic target for EMPD. However, an accurate methodology to determine HER2-positive EMPD has not been established. To assess the optimal methods for detection of HER2-positive EMPD, 73 EMPD samples were analyzed by immunohistochemical (IHC) staining, fluorescence in situ hybridization (FISH), and the HER2 testing algorithm for breast cancer of the American Society of Clinical Oncology/College of American Pathologists, which combined the results of IHC staining and FISH...
May 9, 2018: Medical Oncology
Boubacar Efared, Ibrahim S Sidibé, Sana Gamrani, Ihsane El Otmani, Fatimazahra Erregad, Nawal Hammas, Sanae Bennis, Laila Chbani, Hinde El Fatemi
BACKGROUND: A subset of breast carcinomas harbors overexpression of the human epidermal growth factor receptor 2 (HER2). Fluorescence in situ hybridization (FISH) should be performed in breast carcinomas with equivocal HER2 immunostaining (immunohistochemistry [IHC] HER2 2+). The aim of our study is to investigate clinicopathologic factors associated with HER2 status in breast invasive carcinomas with IHC HER2 2+ through FISH analysis. METHODS: This is a retrospective study including the FISH analysis of 111 patients with invasive breast carcinomas with equivocal HER2 immunostaining...
October 2018: International Journal of Surgical Pathology
Brannan B Griffin, Jennifer L Pincus, Kalliopi P Siziopikou, Luis Z Blanco
Context HER2 status is a prognostic factor and therapeutic target in invasive breast carcinomas. Reflex testing using an alternate method is recommended on equivocal cases via immunohistochemistry or fluorescence in situ hybridization (FISH). Therapeutic dilemmas arise when both tests are equivocal. The standard chromosome 17 centromere reference probe (CEP17) is in close proximity to the HER2 locus and may be coamplified, leading to equivocal results. Alternate chromosome 17 reference probes may aid in establishing the true HER2 status...
March 29, 2018: Archives of Pathology & Laboratory Medicine
Sally Agersborg, Christopher Mixon, Thanh Nguyen, Sramila Aithal, Sucha Sudarsanam, Forrest Blocker, Lawrence Weiss, Robert Gasparini, Shiping Jiang, Wayne Chen, Gregory Hess, Maher Albitar
PURPOSE: While HER2 testing is well established in directing appropriate treatment for breast cancer, a small percentage of cases show equivocal results by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Alternative probes may be used in equivocal cases. We present a single community-based institution's experience in further evaluating these cases. PATIENTS AND METHODS: Between 2014 and 2016, 4255 samples were submitted for HER2 amplification testing by alternative probes, TP53, RAI1, and RARA...
July 2018: Breast Cancer Research and Treatment
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