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Determination of HER2 and p53 Mutations by Sequence Analysis Method and EGFR/Chromosome 7 Gene Status by Fluorescence in Situ Hybridization for the Predilection of Targeted Therapy Modalities in Immunohistochemically Triple Negative Breast Carcinomas in Turkish Population

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Pathology & Oncology Research

Abstract

Triple negative breast cancer (TNBC), an agressive subtype accounts nearly 15 % of all breast carcinomas. Conventional chemotherapy is the only treatment modality thus new, effective targeted therapy methods have been investigated. Epidermal growth factor receptor (EGFR) inhibitors give hope according to the recent studies results. Also therapeutic agents have been tried against aberrant p53 signal activity as TNBC show high p53 mutation rates. Our aim was to detect the incidence of mutations/amplifications identified in TNBC in our population. Here we used sequence analysis to detect HER2 (exon 18–23), p53 (exon 5–8) mutations; fluorescence in situ hybridization (FISH) method to analyse EGFR/chromosome 7 centromere gene status in 82 immunohistochemically TNBC. Basaloid phenotype was identified in 49 (59.8 %) patients. EGFR amplification was noted in 5 cases (6.1 %). All EGFR amplified cases showed EGFR overexpression by immunohistochemistry (IHC). p53 mutations were identified in 33 (40.2 %) cases. Almost 60 % of the basal like breast cancer cases showed p53 mutation. Only one case showed HER2 mutation (exon 20:g.36830_3). Our results showed that gene amplification is not the unique mechanism in EGFR overexpression. IHC might be used in the decision of anti-EGFR therapy in routine practice. p53 mutation rate was lower than the rates reported in the literature probably due to ethnic differences and low sensitivity of sanger sequences in general mutation screening. We also established the rarity of HER2 mutation in TNBC. In conclusion EGFR and p53 are the major targets in TNBC also for our population.

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Acknowledgments

None of the parts of this research article entitled as ‘Determination of HER2 and p53 Mutations by Sequence Analysis Method and EGFR/Chromosome 7 Gene Status by Fluorescence in Situ Hybridization for the Predilection of Targeted Therapy Modalities in Immunohistochemically Triple Negative Breast Carcinomas: Results from Turkish Population’ has had prior or duplicate publication or submission elsewhere. The manuscript has been read and approved by all authors and the requirements for authorship have been met. Furthermore, each author believes that the manuscript represents honest work The authors has no conflict of interest.

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Authors and Affiliations

  1. Izmir Tepecik Training and Research Hospital Pathology Department, Gaziler Caddesi, Yenisehir, Izmir, 35000, Turkey

    Emel Ebru Pala, Umit Bayol, Elif Usturali Keskin, Alp Ozguzer & Ulku Kucuk

  2. Izmir Tepecik Training and Research Hospital, Genetic Department, Izmir, Turkey

    Ozge Ozer & Altug Koc

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  1. Emel Ebru Pala
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  2. Umit Bayol
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  3. Elif Usturali Keskin
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Correspondence to Emel Ebru Pala.

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Pala, E.E., Bayol, U., Keskin, E.U. et al. Determination of HER2 and p53 Mutations by Sequence Analysis Method and EGFR/Chromosome 7 Gene Status by Fluorescence in Situ Hybridization for the Predilection of Targeted Therapy Modalities in Immunohistochemically Triple Negative Breast Carcinomas in Turkish Population. Pathol. Oncol. Res. 21, 1223–1227 (2015). https://doi.org/10.1007/s12253-015-9956-1

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