Prognostic significance of inflammatory factors expression by stroma from breast carcinomas

• Published in: Carcinogenesis (New York) Vol. 37; no. 8; pp. 768 - 776
• Main Authors: Fernandez-Garcia, Belen, Eiro, Noemi, Miranda, Maria-Angeles, Cid, Sandra, González, Luis O, Domínguez, Francisco, Vizoso, Francisco J
• Format: Journal Article
• Language: English
• Published: England 01.08.2016
• Subjects: Adult; Aged; Biomarkers, Tumor - biosynthesis; Biomarkers, Tumor - genetics; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer-Associated Fibroblasts - metabolism; Disease-Free Survival; Female; Gene Expression Regulation, Neoplastic; Humans; Interferon-beta - biosynthesis; Interferon-beta - genetics; Interleukin-10 - biosynthesis; Interleukin-10 - genetics; Interleukin-17 - biosynthesis; Interleukin-17 - genetics; Interleukin-1beta - biosynthesis; Interleukin-1beta - genetics; Interleukin-6 - biosynthesis; Interleukin-6 - genetics; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - pathology; Middle Aged; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - pathology; NF-kappa B - biosynthesis; NF-kappa B - genetics; Prognosis
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgw062

The aim of this work was to evaluate the expression and clinical relevance of some cytokines in breast carcinomas. An immunohistochemical study using tissue arrays and specific antibodies against interleukin 1β (IL-1β), IL-6, IL-10, IL-17, interferon β (IFNβ) and nuclear factor kappa B (NFκB) was performed in 108 breast carcinomas. Most studied cytokines were mainly expressed by cancer cells but also by stromal cells as cancer-associated fibroblasts (CAFs) or mononuclear inflammatory cells (MICs). Global expression (score) of IL-1β and IL-17 was positively associated with histological grade; human epidermal growth factor receptor 2-positive tumors showed a higher global expression of IFNβ but a lower global expression of NFκB; and node-negative tumors showed a higher global expression of IL-6. High score of IL-6 was significantly associated with both longer relapse free-survival (RFS) and overall survival (OS). Moreover, the expression of IL-1β by each stromal cells (CAFs and MICs) was significantly associated with both longer RFS and OS, whereas the expression of IL-10 by these cells was significantly associated with both shorter RFS and OS. However, the combination of IL-1β, IL-6 and IL-10 expression by MICs reached an important association with prognosis and improved our previously reported prognostic signification based on the matrix metalloprotease 11 status by MICs. The combination of IL-1β, IL-6 and IL-10 expression by MICs was significant and independently associated with distant RFS in a multivariate analysis. Therefore, the combination of the expression of IL-1β, IL-6 and IL-10 may serve as promising biomarkers of MICs with prognostic significance, contributing to a better characterization of breast carcinomas microenvironment.