Clinical role of HER2 gene amplification and chromosome 17: a study on 154 IHC-equivocal cases of invasive breast carcinoma patients

Tumor Biology ◽  
2016 ◽  
Vol 37 (7) ◽  
pp. 8665-8672 ◽  
Author(s):  
Muhammad Afzal ◽  
Mohammed Amir ◽  
Muhammad Jawad Hassan ◽  
Muhammad Sikander Hussain ◽  
Muhammad Naveed Aziz ◽  
...  
Tumor Biology ◽  
2016 ◽  
Vol 37 (11) ◽  
pp. 15341-15341
Author(s):  
Muhammad Afzal ◽  
Mohammed Amir ◽  
Muhammad Jawad Hassan ◽  
Muhammad Sikander Hussain ◽  
Muhammad Naveed Aziz ◽  
...  

2018 ◽  
Vol 8 (4) ◽  
pp. 13-22
Author(s):  
Thuan Dang Cong ◽  
Lan Le Trong ◽  

Background: To select patients with targeted breast cancer need to accurately determine the status of HER2 gene amplification. Therefore, HER2 gene amplification should be determined by in situ hybridization (ISH) for all of cases which HER2 positive (2+) by Immunohistochemistry (IHC) staining. Our study aims to apply IHC and DISH to detect HER2 status and relationship with prognostic factors in breast cancer. Subjects and research methods: Cross-sectional descriptive study; 92 patients were diagnosed with invasive breast carcinoma at Hue University Hospital and Hue Central Hospital. IHC and DISH are performed on the Benchmark machines (Ventana) of Roche Diagnostics. Molecular subtypes based on the classification of Saint Gallen (2011). Results: Tumor is usually located in the right breast (53.3%); tumor size > 2-5cm (46.7%); Invasive carcinoma not otherwise specified (73.9%); lymph node metastasis 59.8%, histologic grade 2 (60.3%); disease stage II (51.1%). ER (+) 42.4%, PR (+) 41.3%, HER2 (+) 34.8%, Ki67 (+) 59.8% of cases. The most common molecular subtype of breast cancer is Luminal B (28.3%). HER2 gene amplified by DISH in HER2 (2+) 46.2%, HER2 (3+) by 100%. HER2 gene amplification is associated with HER2 protein expression, molecular subtypes; There is no relationship with the disease stage. Conclusion: In addition to immunohistochemistry, gene amplification with DISH is useful for determining the status of the HER2 gene and supporting the accurate grouping molecular subtypes of breast cancer and target therapy. 34.8% HER2 positive by IHC staining; HER2 gene amplified by DISH in 46.2% of HER2 (2+) cases. There are relationship between the HER2 gene amplified and HER2 protein expression, molecular subtypes in invasive breast carcinoma. Key words: invasive breast cancer, immunohistochemistry, histologic grade, disease stage, molecular subtypes, Dual In Situ Hybridization, DISH


2002 ◽  
Vol 15 (6) ◽  
pp. 657-665 ◽  
Author(s):  
Jianxin Zhao ◽  
Rina Wu ◽  
Alfred Au ◽  
Abbey Marquez ◽  
Yibing Yu ◽  
...  

2008 ◽  
Vol 53 (11) ◽  
pp. 3026-3032 ◽  
Author(s):  
Saima Sharif ◽  
Ramesh K. Ramanathan ◽  
Douglas Potter ◽  
Kathleen Cieply ◽  
Alyssa M. Krasinskas

2018 ◽  
Author(s):  
Falk Zakrzewski ◽  
Walter de Back ◽  
Martin Weigert ◽  
Torsten Wenke ◽  
Silke Zeugner ◽  
...  

AbstractThe human epidermal growth factor receptor 2 (HER2) gene amplification status is a crucial marker for evaluating clinical therapies of breast or gastric cancer. We propose a deep learning-based pipeline for the detection, localization and classification of interphase nuclei depending on their HER2 gene amplification state in Fluorescence in situ hybridization (FISH) images. Our pipeline combines two RetinaNet-based object localization networks which are trained (1) to detect and classify interphase nuclei into distinct classes normal, low-grade and high-grade and (2) to detect and classify FISH signals into distinct classes HER2 or centromere of chromosome 17 (CEN17). By independently classifying each nucleus twice, the two-step pipeline provides both robustness and interpretability for the automated detection of the HER2 amplification status. The accuracy of our deep learning-based pipeline is on par with that of three pathologists and FISH images on a set of 57 validation images containing several hundreds of nuclei are accurately classified. The automatic pipeline is a first step towards assisting pathologists in evaluating the HER2 status of tumors using FISH images, for analyzing FISH images in retrospective studies, and for optimizing the documentation of each tumor sample by automatically annotating and reporting of the HER2 gene amplification specificities.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 474-474 ◽  
Author(s):  
Cecilia Barbara ◽  
Vittoria Martin ◽  
Francesca Molinari ◽  
Lorenza Landi ◽  
Alice Riva ◽  
...  

474 Background: KRAS mutation represents the only validated biomarker used in clinical practice for selection of metastatic colorectal cancer (mCRC) candidates for therapy with the anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibodies. Previous studies conducted in small cohorts of patients suggested that HER2, the major EGFR partner, could modify the sensitivity to anti-EGFR agents. Aim of the present study was to investigate the role of HER2 gene status in a cohort of mCRC patients treated with cetuximab or panitumumab. Methods: 266 chemorefractory mCRC patients treated with cetuximab or panitumumab alone or in combination with chemotherapy were collected in an international consortium effort. HER2 gene status was analyzed using the dual-color FISH assay LSI HER2/neu-CEP17 (PATHVYSION, Abbott) in one central lab, whereas KRAS/BRAF mutations were investigated locally. HER2 gene amplification was defined as the presence of a ratio between HER2 gene and chromosome 17 centromere > 2. Results: An objective response to anti-EGFR therapy (complete or partial response according to RECIST criteria) was observed in 79/266 (29%) of patients. Twelve cases (4.5%) showed the classical pattern of HER2 gene amplification (R>2) in the whole tissue (>80% of tumor cells). By matching HER2 gene status with clinical response we observed that HER2 gene amplification was significantly related to therapy resistance (p<0.0001). Moreover, analysis of follow-up data indicated that HER2 gene amplification was significantly associated with a worse progression free survival (PFS, p=0.0025) and with a trend for a worse overall survival (p=0.062). Similar associations were also observed in the KRAS/BRAF wild-type patients. Conclusions: Data from this large retrospective study suggest that HER2 gene status evaluated by FISH may represent an additional marker useful for the prediction of mCRC patients’ response to EGFR-targeted therapies, in line with very recent evidence. In particular, patients with HER2 gene amplification seem to be resistant and show a shorter PFS. Future studies are needed to deeply investigate the clinical and biological meaning of HER2 gene status deregulation in mCRC.


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