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her2 equivocal

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...
July 30, 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...
July 3, 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...
June 19, 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...
April 1, 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
Weihua Li, Tian Qiu, Yun Ling, Shugeng Gao, Jianming Ying
Next-generation sequencing (NGS) has recently been rapidly adopted in the molecular diagnosis of cancer, but it still faces some obstacles. In this study, 665 lung adenocarcinoma samples (558 TKI-naive and 107 TKI-relapsed samples) were interrogated using NGS, and the challenges and possible solutions of subjecting appropriate tissue samples to NGS testing were explored. The results showed that lower frequencies of HER2/BRAF/PIK3CA and acquired EGFR T790M mutations were observed in biopsy samples with <20% tumor cellularity than in those with ≥20%, but there were no significant differences in the frequencies of EGFR or KRAS mutations...
May 2018: Molecular Oncology
Gary H Tozbikian, Debra L Zynger
In breast cancer, human epidermal growth factor receptor 2 (HER2) status is determined by immunohistochemistry (IHC) and/or in situ hybridization. Oncotype DX also reports HER2 status by an rt-PCR-based assay. Assay concordance between IHC and fluorescent in situ hybridization (FISH) (including alternative probe HER2 FISH) vs Oncotype DX HER2 rt-PCR has not been described in the post-2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) HER2 Guideline revision setting. We performed a retrospective review of HER2 equivocal invasive breast carcinoma from 2014 to 2016 with the Oncotype DX HER2 result...
July 2018: Breast Journal
Joris P Bulte, Altuna Halilovic, Shona Kalkman, Patricia H J van Cleef, Paul J van Diest, Luc J A Strobbe, Johannes H W de Wilt, Peter Bult
AIMS: To establish whether core needle biopsy (CNB) specimens processed with an accelerated processing method with short fixation time can be used to determine accurately the human epidermal growth factor receptor 2 (HER2) status of breast cancer. METHODS AND RESULTS: A consecutive case-series from two high-volume breast clinics was created. We compared routine HER2 immunohistochemistry (IHC) assessment between accelerated processing CNB specimens and routinely processed postoperative excision specimens...
July 2018: Histopathology
Lesley Fallowfield, Lucy Matthews, Shirley May, Valerie Jenkins, David Bloomfield
OBJECTIVE: Chemotherapy side-effects can be substantial. There is increasing recognition that some oestrogen receptor positive (ER +ve), human epidermal growth factor receptor 2 negative (HER2 -ve) patients with breast cancer derive no benefit from chemotherapy and experience only iatrogenic harm. Gene expression profiling tests help refine recurrence risk and likely chemotherapy benefit. EndoPredict® is one such test, which classifies risks of distant recurrence as low or high in patients treated with surgery and adjuvant endocrine therapy alone...
April 2018: Psycho-oncology
Endale Hadgu, Daniel Seifu, Wondemagegnhu Tigneh, Yonas Bokretsion, Abebe Bekele, Markos Abebe, Thomas Sollie, Sofia D Merajver, Christina Karlsson, Mats G Karlsson
BACKGROUND: Breast cancer is a heterogeneous disease with several morphological and molecular subtypes. Widely accepted molecular classification system uses assessment of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation marker Ki67. Few studies have been conducted on the incidence and molecular types of breast cancer in Sub-Saharan Africa. Previous studies mainly from Western and Central Africa, showed breast cancer to occur at younger ages and to present with aggressive features, such as high-grade, advanced stage and triple-negative phenotype (negative for ER, PR and HER2)...
February 14, 2018: BMC Women's Health
Chiara C Volpi, Ambra V Gualeni, Filippo Pietrantonio, Emanuela Vaccher, Antonino Carbone, Annunziata Gloghini
Bright-field in situ hybridization (ISH) methods detect gene alterations that may improve diagnostic precision and personalized management of cancer patients. Areas covered: This review focuses on some bright-field ISH techniques for detection of gene amplification or viral infection that have already been introduced in tumor pathology, research and diagnostic practice. Other emerging ISH methods, for the detection of translocation, mRNA and microRNA have recently been developed and need both an optimization and analytical validation...
March 2018: Expert Review of Molecular Diagnostics
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