July, 2019/ Vol 5/ Issue 7 Print ISSN: 2456-9887, Online ISSN: 2456-1487 Original Research Article Pathology Update: Tropical Journal of Pathology & Microbiology Available online at: www.medresearch.in 479 | Page HER2/neu status detection in breast carcinoma: Is FISH the preferred approach over IHC Harit A.P. 1 , Udupa C.B.K. 2 , Udupa K.S. 3 , Randolph J. 4 , Gopika 5 , Galligan A. 6 1 Attiya P. Harit, USF Morsani College of Medicine- Tampa, FL, USA, 2 Chethana Babu K. Udupa, Department of Pathology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India, 3 Karthik S. Udupa, Department of Medical Oncology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India, 4 Jackson Randolph, USF Morsani College of Medicine-Tampa, FL, USA, 5 Gopika, SR, Pharmacy, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India, 6 Andrew Galligan, USF Morsani College of Medicine-Tampa, FL, USA. Corresponding Author: Chethana Babu K. Udupa, Department of Pathology, Assistant Professor, Kasturba Medical College, Manipal, Manipal Academy of Higher Education (MAHE) Manipal, Karnataka, India. E-mail: chethanababu.ps@gmail.com ………………………………………………………………………………………………………………………………... Abstract Background: HER2/neu amplification is found in 15-30% of all breast cancer patients, which can be detected by either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH). The concordance of FISH and IHC analysis for HER2/neu amplification remains limited, especially with studies in the Indian population. There is a need to further classify this information as HER2/neu positive patients often have a worse disease prognosis and require anti-HER2/neu therapy. Methods: In a retrospective study 149 patients with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC), who underwent both IHC and FISH testing for HER2/neu amplification were analysed to determine the concordance between the two tests in this population. Results: Out of 149 patients reviewed, 58 had equivocal results on IHC, 52 patients had negative results and 39 patients had positive results on IHC. Analysis of the 91 non-equivocal IHC cases and their FISH results demonstrated an inter-rater reliability of Kappa= 0.606 (p <0.0005) 95% CI (0.445, 0.767). Of the 52 patients with negative IHC scores, 13 (25%) were found to be positive on FISH testing for HER/neu amplification. This represents a substantial number of patients who otherwise would not have received anti-HER2/neu therapy. Conclusions: The present results indicate that FISH testing for HER2/neu status should be done on all breast cancer patients whenever possible, irrespective of IHC score status so that appropriate treatment decisions can be made. The higher sensitivity and specificity of FISH testing can reduce the number of both false positive and false negatives seen with immunohistochemistry testing in the present study. Keywords: Breast malignancy, HER2/neu status, Fluorescence In Situ Hybridization ………………………………………………………………………………………………………………………………... Background Breast cancer remains the second most common cancer in Indian women and the leading cause of cancer in urban populations in India with limited data on HER2/neu amplification [2]. The status of HER2/neu gene amplification and over expression is critical in determining the treatment for breast cancer patients, especially for evaluating the role of anti-HER2/ neutherapy. HER2/neu amplification has been associated with a poor prognosis due to the activation of the growth- signaling pathway that leads to tumor cell proliferation. Manuscript received: 18 th June 2019 Reviewed: 28 th June 2019 Author Corrected: 5 th July 2019 Accepted for Publication: 9 th July 2019 Trastuzumab and other anti-HER2/neu therapies have been proven to be an effective treatment for HER2/neu positive breast cancer patients [3]. Screening programmes for HER2/ neu expression in breast carcinoma patients has also been proven to reduce the cost of therapy [4]. In 2013, the American Society of Clinical Oncology/ College of American Pathologists (ASCO/CAP) updated the guidelines for testing HER2/neu amplification in breast cancer. A study on the impact of these modified cut-offs revealed a 2% increase in overall HER2/neupositivity at their institution [5]. Current guidelines recommend testing for HER2/neuamplification for all invasive breast cancers with fluorescence in situ hybridization that are equivocal on immunohistochemical analysis [3].