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Tumor Biology

, Volume 37, Issue 7, pp 8665–8672 | Cite as

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

  • Muhammad Afzal
  • Mohammed Amir
  • Muhammad Jawad Hassan
  • Muhammad Sikander Hussain
  • Muhammad Naveed Aziz
  • Sheeba Murad
  • Iram Murtaza
  • Mariam Anees
  • Aneesa Sultan
Research Article

Abstract

Accurate evaluation of human epidermal growth factor receptor 2 (HER2) status is quite crucial for invasive breast tumor patients in order to select anti-HER2 therapy for effective clinical outcomes. Immunohistochemistry (IHC) assay is routinely used to evaluate the HER2 oncoprotein overexpression but is unable to explain the chromosomal and genetic alterations and has been considered as a hot issue in IHC-equivocal cases. We investigated these molecular aberrations in correlation with prognostic factors. A cohort of 154 IHC-equivocal (+2) cases was selected and retrospectively analyzed by dual-probe fluorescence in situ hybridization (FISH) assay by using locus-specific HER2 and centromere enumeration probes (CEP17) for the identification of HER2 proto-oncogene amplification and chromosomal copy number per cell, respectively. The data were analyzed by SPSS 16.0 version using chi-square test (p < 0.05). We identified 36 out of 154 cases (23.4 %) showing HER2 gene amplification (average HER2 gene copies per cell >4 or <4 with HER2/CEP17 ratio >2) in concordance with HER2 oncoprotein overexpression, and significant correlation was observed with prognostic parameters including histological type, tumor grade II to III, histology and pathological type, lymphatic invasion, ductal carcinoma in situ (DCIS), and estrogen-positive and progesterone-negative receptors. Of the 154 cases, 18 cases (11.7 %) showed polysomy 17 with CEP17 probe signals per cell ≥3 and 22 cases (14.3 %) presented monosomy 17 (CEP17 probe signals per cell ≤1). Our data indicate that the use of anti-HER2 therapy should not be suggested unless true evaluation of HER2 protein expression is made regarding gene amplification essentially in IHC-ambiguous invasive breast tumors.

Keywords

HER2 Breast cancer Prognosis Dual-probe fluorescent in situ hybridization FISH 

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Muhammad Afzal
    • 1
    • 2
  • Mohammed Amir
    • 2
  • Muhammad Jawad Hassan
    • 3
  • Muhammad Sikander Hussain
    • 1
  • Muhammad Naveed Aziz
    • 1
  • Sheeba Murad
    • 3
  • Iram Murtaza
    • 1
  • Mariam Anees
    • 1
  • Aneesa Sultan
    • 1
  1. 1.Department of BiochemistryQuaid-i-Azam UniversityIslamabadPakistan
  2. 2.Shifa International HospitalIslamabadPakistan
  3. 3.Atta-ur-Rehman School of Applied BioSciences (ASAB)National University of Science and Technology (NUST)IslamabadPakistan

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