P1.27 Lung Tumors to Brain Metastases: Do Micrornas Play a Prognostic Role?

Abstract

ABSTRACT More than 50% of cerebral tumors are metastatic in origin. Lung cancer is the most frequently diagnosed malignant tumor and the leading cause of cancer related mortality around the world. Non-small-cell lung cancer (NSCLC), account for 85% of all lung cancer and cerebral metastases from NSCLC are diagnosed in 30-50% of patients, significantly affecting the morbility and mortality. Both the molecular characteristics of the metastatic cells and the microenvironment of the Central Nervous System (CNS) seem to play a relevant role to favor their survival, their growth and their resistance to systemic therapies. The appearance of secondary brain lesions is a complex multi-step process genetically mediated through the inactivation of tumor suppressor genes and activation of oncogens. Currently few instruments are available to identify patients who potentially present major risks to develop brain metastases. Certain miRNAs have been involved as promoters or suppressors of oncogenes and there is growing evidence that their activity may also play a crucial role in developing tumor metastasis possibly influencing multiple aspects of the “metastatic cascade”like cell migration, invasion and extravasation. Therefore, characterization and identification of differences between molecular signature of expression of miRNAs in normal tissue, tumoral and metastatic cells may be important to elucidate the specific role of different miRNAs in development of tumors and to identify the gene and the signal sequences which they control. The aim of our study was to analyze and compare, in a matched series of FFPE tissues from patients affected by NSCLC, the miRNAs expression profiles of primitive tumors and their matched brain metastases. The goals were: a) to select miRNAs whose expression could be correlated to an increased risk to develop cerebral metastases; b) to identify differences between primitive and metastatic tumor tissues which may explain this secondary diffusion and therefore display a prognostic significance. The results obtained from these analysis will be discussed.