Objectives: We compared the performance of two Food and Drug Administration-approved HER2 immunohistochemistry (IHC) tests: HercepTest (Dako) and PATHWAY anti-HER2 (4B5) (Ventana).
Materials And Methods: In total, 180 invasive breast carcinomas previously tested by both HercepTest and fluorescent in situ hybridization (FISH) were retested with 4B5. Three pathologists scored the HER2 IHC using the 2013 American Society of Clinical Oncology/College of American Pathologists guidelines. The HER2 IHC results were correlated with FISH.
Results: Among 135 equivocal cases by HercepTest, 100 (74.1%) were negative by 4B5. Among 45 positive HercepTest cases 9 (20%) were equivocal by 4B5. Among 135 equivocal HercepTest results, 100 (74.1%) were nonamplified, 18 (13.3%) equivocal, and 17 (12.6%) amplified by FISH. Among the 45 positive results with HercepTest, 2 (4.5%) were nonamplified and 1 (2.2%) was equivocal by FISH. All 37 positive and 3 negative by 4B5 cases were amplified by FISH. The absolute interobserver agreement was high for both tests (Fleiss kappa=0.838 for HercepTest and 0.771 for 4B5).
Conclusions: PATHWAY anti-HER2 (4B5) significantly reduced the number of equivocal results that require additional testing. Although HercepTest was positive in a small number of HER2 nonamplified cases, 4B5 failed to detect 3 cases that were interpreted as positive by FISH, all with nonclassic or low levels of amplification.
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Biochem Biophys Res Commun
December 2024
Moscow Center for Advanced Studies, Kulakova Str. 20, 123592, Moscow, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya St., 117997, Moscow, Russia. Electronic address:
Molecular targeted cancer therapy is a rapidly developing field, driving progress toward greater treatment efficacy. However, targeted monotherapy often fails due to the development of multidrug resistance in tumors. The combination of multiple targeted agents emerges as a possible solution to enhance treatment outcomes by activating different signaling pathways.
View Article and Find Full Text PDFEur J Cell Biol
December 2024
Université de Reims Champagne-Ardenne, INSERM, P3Cell, UMR-S 1250, Reims, France. Electronic address:
The tumor suppressor fragile histidine triad (FHIT) is frequently lost in non-small cell lung cancer (NSCLC). We previously showed that a down-regulation of FHIT causes an up-regulation of the activity of HER2 associated to an epithelial-mesenchymal transition (EMT) and that lung tumor cells harboring a FHIT/pHER2 phenotype are sensitive to anti-HER2 drugs. Here, we sought to decipher the FHIT-regulated HER2 signaling pathway in NSCLC.
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November 2024
Department of Oncology, The Affiliated Xinghua People's Hospital, Medical School of Yangzhou University, Xinghua, Jiangsu, China.
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December 2024
Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu Province, China; Department of Pharmacy, Affiliated Women's Hospital of Jiangnan University, Wuxi Maternity and Child Health Care Hospital, Wuxi, Jiangsu Province, China. Electronic address:
HER2-positive breast cancer (HER2+ BC) is distinguished by its poor prognosis, propensity for early onset, and high risk of recurrence and metastasis. Consequently, anti-HER2-targeted therapy has emerged as a principal strategy in the treatment of this form of breast cancer. Pyrotinib, a novel irreversible pan-HER2 tyrosine kinase inhibitor, has brought fresh hope to patients with advanced HER2+ breast cancer.
View Article and Find Full Text PDFMed Oncol
November 2024
Department of Medical Oncology, Cancer Center of Zhejiang University, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, Zhejiang, China.
As the first anti-HER2 targeted agent approved by FDA in 1998, Trastuzumab has significantly improved the outcome of patients with HER2 positive metastatic breast cancer. Unfortunately, resistance to trastuzumab is a severe obstacle to its therapeutic efficacy in clinical application, and its mechanism has not yet been fully elucidated. In our study, we found that stabilization of cyclin D3 could be one reason for trastuzumab resistance.
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