Nguyen, Phuong Thao Tien (2019) HER2 sstatus and molecular subtypes of breast carcinoma in Central Vietnam. Doctoral Thesis.
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Background. Breast cancer is the most commonly occurring cancer in the females and the leading cause of cancer deaths in Vietnamese women. Beside the traditional histopathological classification according to the WHO, the genetic and molecular findings in the last decades have introduced a new nomenclature to identify of breast cancers oriented mostly to the functional characteristics of the neoplastic cells and the needs of therapy. Based on these criteria, breast cancers are divided into five main groups according to the expression levels of biomarkers such as estrogen (ER), progesterone receptors (PR), proliferation index (Ki67) and human epidermal growth factor receptor 2 (HER2). Among them, HER2 protein overexpression and gene amplification have a particularly important role to play in the classification of molecular subtypes. It is also a significant biomarker which has prognostic and predictive value and is a goal of targeted therapy. The aim of this study was to identify the prevalence rate of HER2 gene amplification or overexpression in the local Vietnamese population, and determine the molecular subtypes of breast cancer.
Materials and methods. Paraffin tissue blocks from 88 Vietnamese women diagnosed consecutively with invasive primary breast carcinoma during a period of 12 months, from April 2016 to April 2017. These blocks underwent immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) and dual in situ hybridization (DISH) for the assessment of HER2 status. HER2 positive includes the HER2 (3+) score in IHC or the HER2 gene amplification in FISH. The IHC for ER, PR and Ki67 were also evaluated to determine molecular subtypes. The analyses were based on the guideline of ASCO/CAP 2013.
Results. The median age of patients was 52.5. By using IHC, 30.7 % of tumours were strongly expressed in (3+) score the HER2 protein. The HER2 equivocal results occupied 9.1%. Gene amplification by FISH was found in 25% of tumours with an equivocal score in IHC. The prevalence rate of HER2 positive was 32.9%. The concordance between IHC and DISH assay were 100% in case of IHC positive or negative. In case HER2 results by using immunohistochemistry technique were equivocal, DISH was able to identify 2 cases (25% of cases) as positive. The concordance between FISH and DISH in the equivocal cases was 100%. Luminal B subtype accounted for the highest proportion, at 37.5% whereas luminal A was the lowest, at 18.2%. The HER2 enriched and triple negative subtype occupied 22.7% and 21.6%, respectively. A significant relationship was found between HER2 status as well as molecular subtypes and some clinicopathological characteristics and biomarkers.
Conclusion. HER2 gene amplification was found in 32.9% of Vietnamese breast cancers. This prevalence was considerably higher than in published studies on women from Western countries. Luminal B subtype was the most frequent, at 37.5% while the uncommon belonged to luminal A, at 18.2%. The HER2 enrich and triple negative subtypes were fairly higher than that in literature. HER2 status as well as molecular classification had prognostic and therapeutical significance.
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