Tumor-Associated Macrophages and Tumor-Infiltrating CD8+ Lymphocytes in Breast Cancer: Its Association with Epithlelial-Mesenchymal Transition and Breast Cancer Stem Cell Phenotype
Yoomi Choi, Dong Il Kim, Eun Joo Kim, So Yeon Park. Seoul National University Hospital, Seoul, Republic of Korea; Seoul National University Bundang Hospital, Seongnam, Republic of Korea; Seoul National University College of Medicine, Seoul, Republic of Korea
Background: Recent studies have shown that immune response to tumor can promote epithelial-mesenchymal transition (EMT) and generate cancer stem cells (CSC). Moreover, it has been associated with clinical outcome of breast cancer. In this study, we evaluated the association of tumor-associated macrophages (TAM) and tumor-infiltrating cytotoxic T lymphocytes (CTL) with clinicopathologic features of breast cancer including EMT, CSC phenotype and clinical outcome of the patients.
Design: CD68+ TAM and CD8+ CTL were assessed in tumor nests (intra-tumoral) and in stroma adjacent to tumor cell nests (peri-tumoral) by immunohistochemical staining of tissue microarrays from 170 invasive breast cancers. The expression of EMT-related (Vimentin, N-cadherin, E-cadherin) or CSC markers (CD44+/CD24-, ALDH1) was also assessed.
Results: Infiltration of intra-tumoral and peri-tumoral TAM was significantly correlated with high histologic grade, high proliferation index, vimentin expression. Moreover, peri-tumoral TAM was associated with ALDH1 and N-cadherin expression, and p53 overexpresssion. Presence of intra-tumoral and peri-tumoral CTL was associated with high histologic grade, basal-like subtype, vimentin expression and E-cadherin loss. Especially, intra-tumoral CTL was associated with presence of CD44+/CD24- cells in tumor. In survival analyses, the patients with high level of intra-tumoral TAM tended to have short disease-free survival.
Conclusions: Our study shows that infiltration of TAM and CTL is associated with EMT and CSC phenotype, and is correlated with poor prognostic factors of breast cancer, suggesting potential roles of immune response in the development of aggressive breast cancer.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 32, Wednesday Morning