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Title:
Differential pattern and prognostic significance of CD4+, FOXP3+ and IL-17+tumor infiltrating lymphocytes in ductal and lobular breast cancers | BMC Cancer
Description:
Background Clinical 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. Methods A 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. Results CD4+ 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). Conclusions Ductal 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.
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Keywords {🔍}
breast, cancer, foxp, cells, pubmed, ductal, google, scholar, article, infiltration, cancers, tumor, cas, lymphocytes, lobular, tils, prognostic, survival, lymphocyte, numbers, significantly, patients, total, carcinomas, analysis, data, herneu, tumors, expression, tissue, carcinoma, intratumoral, cell, high, infiltrating, basel, histological, grade, higher, regulatory, human, res, tumorinfiltrating, staining, increased, foxpcd, prognosis, figure, central, clinical,
Topics {✒️}
open access article pre-publication history t-cell-derived cytokine hypoxia-inducible factor-1alpha monoclonal anti-human cd163 paraffin-embedded tissue blocks 40x high-power-field early-onset breast carcinomas t-lymphocytes subsets endowed vitro-induced foxp3+cd8+ human tumor-specific cd8 inti zlobec tumor-infiltrating lymphocytes isolated unfavourable clinico-pathological features regulatory cd4+ t-cells author information authors article download pdf tumour-infiltrating lymphocytes cd4+ t-cells infiltration kaplan-meier survival curves b7-h1+/pd-1+ tumor-infiltrating lymphocyte subtype triple negative cancer il-17+tumor infiltrating lymphocytes tumor-infiltrating foxp3+ regulatory triple negative ductal t-cell subsets full access ductal carcinoma appears anti-cd4 antibody tumor suppressor gene t-cells expressing privacy choices/manage cookies anti-foxp3 antibody t-cell infiltration lymph node metastases human breast cancer adaptive immune system coya tapia pancreatic carcinoma cells breast cancer samples small breast cancers positive breast cancer early breast cancer lobular breast cancer expressing lobular carcinomas de andrade jm positive lymph nodes reliable treg markers human th17 cells
Questions {❓}
- Roncarolo MG, Gregori S: Is FOXP3 a bona fide marker for human regulatory T cells?
- Wilke CM, Kryczek I, Wei S, Zhao E, Wu K, Wang G, et al: Th17 cells in cancer: help or hindrance?
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headline:Differential pattern and prognostic significance of CD4+, FOXP3+ and IL-17+tumor infiltrating lymphocytes in ductal and lobular breast cancers
description:Clinical 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. A 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. CD4+ 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). Ductal 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.
datePublished:2012-04-03T00:00:00Z
dateModified:2012-04-03T00:00:00Z
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keywords:
Breast Cancer
Ductal Carcinoma
Lobular Carcinoma
Tumor Infiltrate Lymphocyte
Ductal Cancer
Cancer Research
Oncology
Surgical Oncology
Health Promotion and Disease Prevention
Biomedicine
general
Medicine/Public Health
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headline:Differential pattern and prognostic significance of CD4+, FOXP3+ and IL-17+tumor infiltrating lymphocytes in ductal and lobular breast cancers
description:Clinical 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. A 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. CD4+ 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). Ductal 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.
datePublished:2012-04-03T00:00:00Z
dateModified:2012-04-03T00:00:00Z
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Breast Cancer
Ductal Carcinoma
Lobular Carcinoma
Tumor Infiltrate Lymphocyte
Ductal Cancer
Cancer Research
Oncology
Surgical Oncology
Health Promotion and Disease Prevention
Biomedicine
general
Medicine/Public Health
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