Histological Analysis of γδ T Lymphocytes Infiltrating Human Triple-Negative Breast Carcinomas.

Jose Villacorta Hidalgo,Annette Schmitt-Graeff,Elmar Stickeler,Marzenna Orlowska-Volk,Liliana B Dã­Az,Peter Bronsert,Martin Werner,Gian Kayser,Miroslav Malkovsky,Paul Fisch

doi:10.3389/fimmu.2014.00632

Abstract

Breast cancer is the leading cause of cancer death in women and the second most common cancer worldwide after lung cancer. The remarkable heterogeneity of breast cancers influences numerous diagnostic, therapeutic, and prognostic factors. Triple-negative breast carcinomas (TNBCs) lack expression of HER2 and the estrogen and progesterone receptors and often contain lymphocytic infiltrates. Most of TNBCs are invasive ductal carcinomas (IDCs) with poor prognosis, whereas prognostically more favorable subtypes such as medullary breast carcinomas (MBCs) are somewhat less frequent. Infiltrating T-cells have been associated with an improved clinical outcome in TNBCs. The prognostic role of γδ T-cells within CD3+ tumor-infiltrating T lymphocytes remains unclear. We analyzed 26 TNBCs, 14 IDCs, and 12 MBCs, using immunohistochemistry for the quantity and patterns of γδ T-cell infiltrates within the tumor microenvironment. In both types of TNBCs, we found higher numbers of γδ T-cells in comparison with normal breast tissues and fibroadenomas. The numbers of infiltrating γδ T-cells were higher in MBCs than in IDCs. γδ T-cells in MBCs were frequently located in direct contact with tumor cells, within the tumor and at its invasive border. In contrast, most γδ T-cells in IDCs were found in clusters within the tumor stroma. These findings could be associated with the fact that the patient’s prognosis in MBCs is better than that in IDCs. Further studies to characterize these γδ T-cells at the molecular and functional level are in progress.

Highlights

Worldwide, breast cancer is the principal cause of cancer related deaths in women in developed and in developing countries [1]
Since the amounts of tumor-infiltrating lymphocytes (TILs) in primary triple-negative breast carcinomas (TNBCs) appear to be associated with prognosis [35], we studied these tumors, focusing on the possibility that immunohistochemistry (IHC) of γδ T-cell infiltration may help our understanding of the substantial prognostic difference between invasive ductal carcinomas (IDCs) and medullary breast carcinomas (MBCs)
The lymphocytic infiltrates in IDCs and MBCs contained many γδ T-cells (Figure 2). Both types of TNBCs, contained conspicuous numbers of γδ T-cells (Table 3), the TCRγδ+ cells within the TILs were more frequently located in the stroma of the IDC sections (Figures 2A,B), while in the MBC sections TCRγδ+ cells were typically located in the tumor parenchyma (Figure 2C) and at the invasive tumor cell border (Figure 2D)

Summary

Introduction

Breast cancer is the principal cause of cancer related deaths in women in developed and in developing countries [1]. Breast cancer is a heterogeneous disease of numerous tumor subtypes with different biological characteristics and clinical prognosis [2]. One subgroup with a poor prognosis are triple-negative breast carcinomas (TNBCs) characterized by lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. TNBCs are generally high-grade tumors and mostly invasive ductal carcinomas (IDCs), other types of breast cancers can be triple negative such as the medullary breast carcinoma (MBC) [5, 6]. MBCs represent only 3–5% of all breast cancers and are characterized by a well-circumscribed margin, a poorly differentiated nuclear grade, a high-mitotic rate, prominent syncytial growth in more than the 75% of the tumor area and a diffuse lymphoid infiltrate without intraductal components or micro-glandular features [7]. The MBC’s aggressive histological characteristics are very similar to those of high-grade triple-negative IDCs, MBCs have generally a remarkably better prognosis than IDCs [7,8,9]

Methods

Results

Conclusion