Interleukins-6 and -11 expression in primary breast cancer and subsequent development of bone metastases

Abstract

Breast cancers frequently metastasize to bone where they often cause extensive tumor-induced osteoclast-mediated osteolysis. Interleukin-6 (IL-6) and IL-11 are two cytokines exhibiting osteolytic properties through their potent stimulation of osteoclast formation. We investigated the expression of IL-6 and IL-11 in 99 invasive primary breast tumors by immunohistochemistry and in situ hybridization, respectively. We examined their potential as predictive factors for further development of bone metastases. 52/90 (57%) of tumor samples showed IL-6 cytoplasmic immunostaining. There was no significant association between IL-6 status and any of the classical prognostic factors. 15/89 (17%) of the tumor samples expressed IL-11 mRNA. A positive IL-11 mRNA status was associated with a low tumor grade (P=0.05). Tumors expressing IL-11 mRNA had a statistically significant (P=0.002) higher rate of bone metastases occurrence (12/15, 80%) than IL-11 negative tumors (27/74, 37%). Such association was not found for IL-6. Our findings demonstrate for the first time IL-11 gene expression in some primary invasive breast tumors and suggest the potential of this cytokine as possible biological predictive factor for the development of bone metastases.