Abstract
BackgroundThe immune system has paradoxical roles during cancer development and the prognostic significance of immune modulating factors is controversial. The aim of this study was to determine the expression of cyclooxygenase 2 (COX-2), transforming growth factor-beta (TGF- beta), interleukin-10 (IL-10) and their prognostic significance in breast cancers. Ki67 was included as a measure of growth fraction of tumor cells.MethodsOn immunohistochemical stained slides from 38 breast cancer patients, we performed digital video analysis of tumor cell areas and adjacent tumor stromal areas from the primary tumors and their corresponding lymph node metastases. COX-2 was recorded as graded staining intensity.ResultsThe expression of TGF-beta, IL-10 and Ki67 were recorded in tumor cell areas and adjacent tumor stromal areas. In both primary tumors and metastases, the expression of COX-2 was higher in the tumor stromal areas than in the tumor cell areas (both P < 0.001). High stromal staining intensity in the primary tumors was associated with a 3.9 (95% CI 1.1-14.2) times higher risk of death compared to the low staining group (P = 0.036). The expression of TGF-beta was highest in the tumor cell areas of both primary tumors and metastases (both P < 0.001). High stromal expression of TGF-beta was associated with increased mortality. For IL-10, the stromal expression was highest in the primary tumors (P < 0.001), whereas in the metastases the expression was highest in tumor cell areas (P < 0.001). High IL-10 expression in tumor- and stromal cell areas of primary tumors predicted mortality. Ki67 was higher expressed in tumor stromal areas of the metastases, and in tumor cell areas of the primary tumors (P < 0.001). Ki67 expression in tumor cell areas and stromal areas of the metastases was independently associated with breast cancer mortality.ConclusionsStromal expression of COX-2, TGF-beta and Ki67 may facilitate tumor progression in breast cancer.
Highlights
The immune system has paradoxical roles during cancer development and the prognostic significance of immune modulating factors is controversial
Desmoplasia in invasive tumors and metastases is morphologically characterized by extensive proliferation of fibroblast-like cells and extracellular matrix (ECM); inflammation and immune responses represented by lymphocytes, macrophages, dendritic cells; and tumor angiogenesis [15]
We evaluated the prognostic significance of the immunomodulatory signalling molecules cyclooxygenase 2 (COX-2), transforming growth factor-b (TGF-b), IL-10 and Ki67 in tumor epithelium and stromal areas of human breast cancer
Summary
The immune system has paradoxical roles during cancer development and the prognostic significance of immune modulating factors is controversial. The aim of this study was to determine the expression of cyclooxygenase 2 (COX-2), transforming growth factor-beta (TGF- beta), interleukin-10 (IL-10) and their prognostic significance in breast cancers. The cytokine cyclooxygenase-2 (COX-2) is frequently expressed by cancerous cells. It is Not constitutively expressed, but can be rapidly induced by oncogenes, other cytokines, chemokines, growth factors, hypoxia, ultraviolet light, and epidermal growth factors. TGF-b induces a-smooth muscle actin and collagen production in culture fibroblasts [14] and is a potential mediator of desmoplastic responses in tumors. TGF-b is elevated in cancer cells compared to normal epithelial cells, and appears to be even more elevated in poorly differentiated tumors [17,18]
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