en زیست شناسی ملکولی Molecular Biology مقالات اصلی Original Article <div style="text-align: justify;"><strong><em>Background: </em></strong>The aim of this study was to assess the usability of multiplex ligation-dependent probe amplification (MLPA) for copy number determination of <em>HER</em> gene family members (<em>ERBB1-4</em>) in invasive breast carcinoma and to explore the association of <em>ERBB1-4 </em>gene copy numbers with clinicopathological characteristics of breast cancer (BC) patients.<br> <br> <strong><em>Methods:</em></strong> Clinical and immunohistochemical characteristics were assessed in 104 BC patients and the molecular subtype was determined for each tumor sample. Furthermore, HER-2/neu status was assessed by immunohistochemistry (IHC) and equivocal results were confirmed by Fluorescent in situ hybridization (FISH). The copy numbers of <em>ERBB1-4</em> genes were determined by MLPA.<br> <br> <strong><em>Results:</em></strong> Twenty-five percent of all patients showed <em>ERBB2</em> gene-amplification by MLPA, whereas 14.4% of cases showed <a name="OLE_LINK1">ERBB-2/neu </a>overproduction at the protein level (IHC). Moreover, only 2.9% and 1.9% of patients showed amplification in <em>ERBB1</em> and <em>ERBB4</em>, respectively. No copy number changes were observed in <em>ERBB3</em>. Our results indicated a significant association between <em>ERBB2</em> copy number gain and histological grade (<em>p value</em>= 0.01), stage (<em>p value</em>= 0.02), and tumor subtypes (<em>p value</em>= <0.001). In addition, we found MLPA more accurate in assessing <em>HER2</em> status with 15.4% and 9.6% gene amplification detection in early stages (1, 2A and 2B) and advanced tumor stages (3A, 3B, and 4), respectively, compared to IHC (early stages= 13.5% and advanced stages= 4.7%).<br> <br> <strong><em>Conclusions:</em></strong> According to our findings, MLPA is a fast, precise and low-cost technique to detect <em>ERBB2 </em>amplification, especially in advanced tumor stages. However, due to infrequent amplification found in <em>ERBB1</em> and <em>ERBB4</em> as well as the lack of amplification in <em>ERBB3</em>, their importance in the prognostic evaluation of BC patients remains controversial.<br> &nbsp;</div> Breast Cancer, Copy number variation, ERBB1-4, IHC, MLPA. 91 101 http://rbmb.net/browse.php?a_code=A-10-275-1&slc_lang=en&sid=1 Mohsen Soosanabadi soosanabadi@hotmail.com 100319475328460017190 100319475328460017190 No Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. Reza Mirfakhraie reza_mirfakhraie@yahoo.com 100319475328460017191 100319475328460017191 No Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Lilit Atanesyan l.atanesyan@mlpa.com 100319475328460017192 100319475328460017192 No MRC-Holland BV, Amsterdam, the Netherlands Akbar Biglarian abiglarian@gmail.com 100319475328460017193 100319475328460017193 No Department of Biostatistics and Computer Sciences, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. Fatemeh Aghakhani Moghadam shahlamoghadam@hotmail.com 100319475328460017194 100319475328460017194 No Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. Maryam Rahimi maryamrahimi1986@yahoo.com 100319475328460017195 100319475328460017195 No Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. Farkhondeh Behjati lllvllloh3n@gmail.com 100319475328460017196 100319475328460017196 No Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. Elaheh Keyhani ekeyhani1058@gmail.com. 100319475328460017197 100319475328460017197 Yes Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran & Clinical Research Development Center of Rofeideh Rehabilitation Hospital, Tehran, Iran.