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

Autor: Mohammed Amir, Mariam Anees, Muhammad Afzal, Muhammad Naveed Aziz, Sheeba Murad, Iram Murtaza, Muhammad Jawad Hassan, Muhammad Hussain, Aneesa Sultan
Rok vydání: 2016
Předmět:
Adult
0301 basic medicine
Monosomy
Pathology
medicine.medical_specialty
Receptor
ErbB-2
Lymphovascular invasion
Breast Neoplasms
Biology
Proto-Oncogene Mas
03 medical and health sciences
0302 clinical medicine
Breast cancer
Biomarkers
Tumor
medicine
Humans
Neoplasm Invasiveness
skin and connective tissue diseases
In Situ Hybridization
Fluorescence
Aged
Neoplasm Staging
Retrospective Studies
Aged
80 and over
Chromosome Aberrations
Polysomy
medicine.diagnostic_test
Carcinoma
Ductal
Breast
Gene Amplification
General Medicine
Middle Aged
Ductal carcinoma
Prognosis
medicine.disease
Chromosome 17 (human)
Carcinoma
Lobular
Carcinoma
Intraductal
Noninfiltrating
030104 developmental biology
030220 oncology & carcinogenesis
Immunohistochemistry
Female
Neoplasm Grading
Chromosomes
Human
Pair 17
Follow-Up Studies
Fluorescence in situ hybridization
Zdroj: Tumor Biology. 37:8665-8672
ISSN: 1423-0380
1010-4283
DOI: 10.1007/s13277-015-4657-7
Popis: 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 cell4 or4 with HER2/CEP17 ratio2) 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.
Databáze: OpenAIRE
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