[3, 4] This trend could be related to a better histological diagnosis of ICC and/or to the rising incidence of the main risk factors for ICC: cholangitis, chronic hepatitis B and C, diabetes, and obesity.[5] Liver resection remains the only curative treatment for ICC but is associated with a high rate of recurrence.[6] Recently, we showed that hilar lymph node metastasis, perineural invasion, and intrahepatic satellite nodules represent high risk factors for ICC recurrence in patients undergoing liver resection.[7]

For patients with nonresectable ICC, chemotherapies selleck chemicals llc provide only partial benefit.[8, 9] To date, the overall prognosis of patients with ICC is poor, necessitating the identification of accurate prognostic factors and novel therapeutic strategies. Growing evidence demonstrates that tumor onset and progression are determined not only by cancer cells themselves but also by their microenvironment.[10] Microenvironment is a dynamic system which includes

several types of cells (e.g., myo-fibroblasts, immune and endothelial cells), soluble factors (e.g., cytokines), and components of the extracellular matrix (ECM) which constitute the stroma of tumors. Importantly, the stroma modulates key processes of carcinogenesis, including cell communication, differentiation, invasiveness, chemoresistance, and epithelial to mesenchymal transition (EMT). Supporting the dynamic coevolution of tumor cells with their microenvironment, several studies have demonstrated Methocarbamol that stromal gene expression signatures Omipalisib mouse correlated with the progression of cancers.[11-13] In the liver, we have previously shown that ECM remodeling is associated with tumor progression.[14] More recently, we identified a gene signature characteristic of

the tumor-stroma crosstalk that was successful at predicting the survival of patients with hepatocellular carcinoma (HCC).[15] We also showed that targeting the tumor-stroma crosstalk by epigenetic modulators may represent a promising therapeutic strategy in HCC.[15] The presence of a dense stroma is a prominent feature of ICC, suggesting that remodeling of the tumor microenvironment may represent a key process in ICC onset and progression.[16] Thus, we hypothesized that relevant prognostic biomarkers could be inferred by investigating alterations of the stroma in ICC. By laser capture microdissection (LCM), gene expression profiling, and tissue microarray analysis (TMA) we identified a gene signature of the tumor stroma in ICC from which the overexpression of osteopontin was shown to be an independent predictor of overall and disease-free survival. A cohort of 87 patients with primary ICC was studied. These patients underwent liver resection at Rennes-University hospital between January 1997 and August 2011. Only mass-forming types of ICC were included, as defined by the Liver Cancer Study Group of Japan. Written informed consent was obtained from all patients.