title: Clinical role of HER2 gene amplification and chromosome 17: a study on 154 IHC-equivocal cases of invasive breast carcinoma patients.
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.
authors.affiliation: Department of Biochemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan.|Shifa International Hospital, H-8/4, Islamabad, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Afzal
authors.affiliation: Shifa International Hospital, H-8/4, Islamabad, Pakistan.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Amir
authors.affiliation: Atta-ur-Rehman School of Applied BioSciences (ASAB), National University of Science and Technology (NUST), Islamabad, Pakistan.
authors.forename: Muhammad Jawad
authors.initials: MJ
authors.lastname: Hassan
authors.affiliation: Department of Biochemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan.
authors.forename: Muhammad Sikander
authors.initials: MS
authors.lastname: Hussain
authors.affiliation: Department of Biochemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan.
authors.forename: Muhammad Naveed
authors.initials: MN
authors.lastname: Aziz
authors.affiliation: Atta-ur-Rehman School of Applied BioSciences (ASAB), National University of Science and Technology (NUST), Islamabad, Pakistan.
authors.forename: Sheeba
authors.initials: S
authors.lastname: Murad
authors.affiliation: Department of Biochemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan.
authors.forename: Iram
authors.initials: I
authors.lastname: Murtaza
authors.affiliation: Department of Biochemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan.
authors.forename: Mariam
authors.initials: M
authors.lastname: Anees
authors.affiliation: Department of Biochemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan. aneesasultan@gmail.com.
authors.forename: Aneesa
authors.initials: A
authors.lastname: Sultan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human; C508053:ERBB2 protein, human
keywords: Breast cancer; Dual-probe fluorescent in situ hybridization; FISH; HER2; Prognosis