Differential pattern and prognostic significance of CD4+, FOXP3+ and IL-17+tumor infiltrating lymphocytes in ductal and lobular breast cancers

BMC Cancer

Research Article

Uwe Güth¹  Daniel Oertli²  Raoul Droeser³  Ergin Kilic⁴  Coya Tapia⁵  Inti Zlobec⁵  Giulio Spagnoli⁶  Michael Heberer⁶ 

[1] Department of Gynecology and Obstetrics, University Hospital Basel, Spitalstrasse 21, 4056, Basel, Switzerland;Department of Surgery, University Hospital Basel, Spitalstrasse 21, 4031, Basel, Switzerland;Department of Surgery, University Hospital Basel, Spitalstrasse 21, 4031, Basel, Switzerland;Institute for Surgical Research and Hospital Management ICFS and Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031, Basel, Switzerland;Institute for Pathology, Charité University Hospital, Campus-Mitte, Charitéplatz 1, 10117, Berlin, Germany;Institute for Pathology, University Hospital Bern, Murtenstrasse 31, 3010, Bern, Switzerland;Institute for Pathology, University Hospital Basel, Schönbeinstrasse 40, 4031, Basel, Switzerland;Institute for Surgical Research and Hospital Management ICFS and Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031, Basel, Switzerland;

关键词: Breast Cancer;    Ductal Carcinoma;    Lobular Carcinoma;    Tumor Infiltrate Lymphocyte;    Ductal Cancer;   

DOI  :  10.1186/1471-2407-12-134

 received in 2011-05-19, accepted in 2012-04-03,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundClinical relevance of tumor infiltrating lymphocytes (TILs) in breast cancer is controversial. Here, we used a tumor microarray including a large series of ductal and lobular breast cancers with long term follow up data, to analyze clinical impact of TIL expressing specific phenotypes and distribution of TILs within different tumor compartments and in different histological subtypes.MethodsA tissue microarray (TMA) including 894 ductal and 164 lobular breast cancers was stained with antibodies recognizing CD4, FOXP3, and IL-17 by standard immunohistochemical techniques. Lymphocyte counts were correlated with clinico-pathological parameters and survival.ResultsCD4+ lymphocytes were more prevalent than FOXP3+ TILs whereas IL-17+ TILs were rare. Increased numbers of total CD4+ and FOXP3+ TIL were observed in ductal, as compared with lobular carcinomas. High grade (G3) and estrogen receptor (ER) negative ductal carcinomas displayed significantly (p < 0.001) higher CD4+ and FOXP3+ lymphocyte infiltration while her2/neu over-expression in ductal carcinomas was significantly (p < 0.001) associated with higher FOXP3+ TIL counts. In contrast, lymphocyte infiltration was not linked to any clinico-pathological parameters in lobular cancers. In univariate but not in multivariate analysis CD4+ infiltration was associated with significantly shorter survival in patients bearing ductal, but not lobular cancers. However, a FOXP3+/CD4+ ratio > 1 was associated with improved overall survival even in multivariate analysis (p = 0.033).ConclusionsDuctal and lobular breast cancers appear to be infiltrated by different lymphocyte subpopulations. In ductal cancers increased CD4+ and FOXP3+ TIL numbers are associated with more aggressive tumor features. In survival analysis, absolute numbers of TILs do not represent major prognostic indicators in ductal and lobular breast cancer. Remarkably however, a ratio > 1 of total FOXP3+/CD4+ TILs in ductal carcinoma appears to represent an independent favorable prognostic factor.

【 授权许可】

Unknown   
© Droeser et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.