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Oncotarget. 2017 Aug 16;8(44):76974-76986. doi: 10.18632/oncotarget.20293. eCollection 2017 Sep 29.

The prognostic significance of combined androgen receptor, E-Cadherin, Ki67 and CK5/6 expression in patients with triple negative breast cancer.

Author information

1
Department of Medical Oncology, Hospital Clínic of Barcelona, Barcelona, Spain.
2
Medical Oncology Unit A.O. Papardo & Department of Human Pathology University of Messina, Messina, Italy.
3
Department of Human Pathology of Adult and Evolutive Age "Gaetano Barresi", Section of Pathology, University of Messina, AOU Policlinico "G. Martino" Messina, Italy.
4
Pathology Unit, Humanitas Center of Oncology, Catania, Italy.
5
Medical Oncology, Humanitas Catania Oncology Center, Catania, Italy.
6
G. F. Ingrassia Department, Section of Anatomic Pathology, University Hospital "Policlinico-Vittorio Emanuele", Catania, Italy.

Abstract

Background:

Triple Negative Breast Cancer (TNBC) represents a heterogeneous group of tumors with poor prognosis owing to aggressive tumor biology and lack of targeted therapies. No clear prognostic biomarkers have been identified to date for this subgroup.

Materials and Methods:

In this retrospective study we evaluated the prognostic role of 4 different molecular determinants, including androgen receptor (AR), E-cadherin (CDH1), Ki67 index, and basal cytokeratins (CKs) 5/6, in a cohort of 99 patients with TNBC. All patients received neo/adjuvant chemotherapy (mostly anthracycline/taxane-based). Immunohistochemistry (IHC) was performed in formalin-fixed paraffin-embedded primary tumor samples. CDH1 expression was considered positive as ≥ 30% of the membrane cells staining. AR positivity was defined as > 10% of positive tumor cells. High Ki67 was defined as ≥20% positive tumor cells. CK5/6 expression was judged positive if the score was ≥1.

Results:

The absence of AR expression was significantly associated with highly undifferentiated tumors. Univariate analyses showed that lack of expression of CDH1, tumor size and nodal status were significantly correlated with worse RFS and OS (p< 0.05). AR expression and low Ki67 showed a trend towards better RFS and OS. Patients with absent CK5/6 expression in univariate and multivariate analyses had poorer RFS (p=0.02 and p=0.002, respectively) and OS (p=0.05 and p=0.02, respectively). Multivariate analysis showed an independent association between CDH1 expression and better RFS and OS (p< 0.05) beyond tumor size, nodal status, and grade. The Kaplan-Meier curves showed that patients with AR and CDH1 negative expression and high Ki-67 levels have a significant correlation with poor outcome.

Conclusions:

Our study supports the use of IHC expression of AR, CDH1, Ki67, and CK5/6 as prognostic markers in TNBCs and suggests a link between their expression and prognosis and may help to stratify TNBC patients in different prognostic classes.

KEYWORDS:

CK5/6; Ki67; androgen receptor; e-cadherin; triple negative breast cancer

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