Simin Ahmadvand1,2, Zahra Faghih2, Mehdi Montazer3, Akbar Safaei3, Maral Mokhtari3, Peyman Jafari4, Abdol-Rasoul Talei5, Sedigheh Tahmasebi5, Abbas Ghaderi6,7. 1. Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. 2. Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. 3. Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. 4. Department of Biostatistics, Shiraz University of Medical Sciences, Shiraz, Iran. 5. Breast Disease Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. 6. Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. ghaderia@sums.ac.ir. 7. Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. ghaderia@sums.ac.ir.
Abstract
PURPOSE: In recent years, the prognostic/predictive significance of tumor infiltrating lymphocytes (TILs) has become a topic of interest. Here, we aimed to evaluate the prognostic significance of CD3+, CD8+, CD45RO+ and Foxp3+ TILs in breast cancer, as well as the relation of these markers to other clinicopathological features of this disease. METHODS: FFPE tumor samples from 94 females with invasive ductal carcinoma of the breast were retrospectively selected and immunohistochemically assessed for CD3, CD8, CD45RO and Foxp3 expression. Digital photos were acquired from the center (CT) and invasive margins (IM) of the tumors, after which positive cells were counted using ImageJ software. RESULTS: We found that greater infiltrations of target lymphocyte subpopulations were associated with TNM stage III, lymph node metastasis, high histological grade, ER negativity and HER2 positivity. The ratios of CD8+ cytotoxic T cells to CD3+, CD45RO+ and Foxp3+ TILs were found to be relatively higher in tumors exhibiting the aforementioned characteristics. In univariate survival analyses, CD8+ TILs in the IM and total CD45RO+ TILs were found to be significantly associated with overall survival (OS). Infiltration of CD45RO+ TILs in the CT and lymph node status were variables that significantly correlated with disease-free survival (DFS). Multiple Cox regression analyses revealed independent significant prognostic effects of total CD45RO+ TILs and lymph node status (HR of 3.24 and 3.19, respectively) in predicting OS. Infiltration of CD45RO+ TILs in the CT (HR 3.12) and lymph node status (HR 3.15) also exhibited significant prognostic effects on DFS. CONCLUSION: From our data we conclude that CD45RO+ TILs serve as prognostic factors for predicting OS and DFS of breast cancer patients.
PURPOSE: In recent years, the prognostic/predictive significance of tumor infiltrating lymphocytes (TILs) has become a topic of interest. Here, we aimed to evaluate the prognostic significance of CD3+, CD8+, CD45RO+ and Foxp3+ TILs in breast cancer, as well as the relation of these markers to other clinicopathological features of this disease. METHODS: FFPE tumor samples from 94 females with invasive ductal carcinoma of the breast were retrospectively selected and immunohistochemically assessed for CD3, CD8, CD45RO and Foxp3 expression. Digital photos were acquired from the center (CT) and invasive margins (IM) of the tumors, after which positive cells were counted using ImageJ software. RESULTS: We found that greater infiltrations of target lymphocyte subpopulations were associated with TNM stage III, lymph node metastasis, high histological grade, ER negativity and HER2 positivity. The ratios of CD8+ cytotoxic T cells to CD3+, CD45RO+ and Foxp3+ TILs were found to be relatively higher in tumors exhibiting the aforementioned characteristics. In univariate survival analyses, CD8+ TILs in the IM and total CD45RO+ TILs were found to be significantly associated with overall survival (OS). Infiltration of CD45RO+ TILs in the CT and lymph node status were variables that significantly correlated with disease-free survival (DFS). Multiple Cox regression analyses revealed independent significant prognostic effects of total CD45RO+ TILs and lymph node status (HR of 3.24 and 3.19, respectively) in predicting OS. Infiltration of CD45RO+ TILs in the CT (HR 3.12) and lymph node status (HR 3.15) also exhibited significant prognostic effects on DFS. CONCLUSION: From our data we conclude that CD45RO+ TILs serve as prognostic factors for predicting OS and DFS of breast cancerpatients.
Entities:
Keywords:
Breast cancer; CD45RO+ memory T cell; CD8+ cytotoxic T cell; Prognostic marker; Tumor-infiltrating lymphocytes
Authors: Petros X E Mouratidis; Marcia Costa; Ian Rivens; Elizabeth E Repasky; Gail Ter Haar Journal: J R Soc Interface Date: 2021-07-07 Impact factor: 4.118