Immunoprofile from tissue microarrays to stratify familial breast cancer patients

Laura Schirosi, Simona De Summa, Stefania Tommasi, Angelo Paradiso, Domenico Sambiasi, Ondina Popescu, Giovanni Simone, Anita Mangia

Research output: Contribution to journalArticle

Abstract

Familial breast cancer (BC) is a heterogeneous disease with variable prognosis. The identification of an immunoprofile is important to predict tumor behavior for the routine clinical management of familial BC patients. Using immunohistochemistry on tissue microarrays, we studied 95 familial BCs in order to analyze the expression of some biomarkers involved in different pathways. We used unsupervised hierarchical clustering analyses (HCA), performed using the immunohistochemical score data, to define an immunoprofile able to characterize these tumors. The analyses on 95 and then on a subset of 45 tumors with all biomarkers contemporarily evaluable, revealed the same biomarker and patient clusters. Focusing on the 45 tumors we identified a group of patients characterized by the low expression of estrogen receptor (P = 0.009), progesterone receptor (P <0.001), BRCA1 (P = 0.005), nuclear Na+/H+ exchanger regulatory factor 1 (NHERF1) (P = 0.026) and hypoxia inducible factor-1 alpha (P <0.001), and also by the higher expression of MIB1 (P = 0.043), cytoplasmic NHERF1 (P = 0.004), cytoplasmic BRCT-repeat inhibitor of hTERT expression (P = 0.001), vascular endothelial growth factor (VEGF) (P = 0.024) and VEGF receptor-1 (P = 0.029). This immunoprofile identified a more aggressive tumor phenotype associated also with a larger tumor size (P = 0.012) and G3 grade (P = 0.006), confirmed by univariate and multivariate analyses. In conclusion, the clinical application of HCA of immunohistochemical data could allow the assessment of prognostic biomarkers to be used simultaneously. The 10 protein expression panel might be used to identify the more aggressive tumor phenotype in familial BC and to direct patients towards a different clinical therapy.

Original languageEnglish
Pages (from-to)27865-27879
Number of pages15
JournalOncotarget
Volume6
Issue number29
DOIs
Publication statusPublished - 2015

Fingerprint

Biomarkers
Neoplasms
Cluster Analysis
Vascular Endothelial Growth Factor Receptor-1
Phenotype
Hypoxia-Inducible Factor 1
Progesterone Receptors
Familial Breast Cancer
Estrogen Receptors
Vascular Endothelial Growth Factor A
Multivariate Analysis
Immunohistochemistry
Proteins
sodium-hydrogen exchanger regulatory factor
Therapeutics

Keywords

  • Familial breast cancer
  • Hierarchical clustering analysis
  • Immunoprofile
  • TMA

ASJC Scopus subject areas

  • Oncology

Cite this

Immunoprofile from tissue microarrays to stratify familial breast cancer patients. / Schirosi, Laura; De Summa, Simona; Tommasi, Stefania; Paradiso, Angelo; Sambiasi, Domenico; Popescu, Ondina; Simone, Giovanni; Mangia, Anita.

In: Oncotarget, Vol. 6, No. 29, 2015, p. 27865-27879.

Research output: Contribution to journalArticle

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