Clusterin in stool: A new diagnostic marker of colorectal cancer

Abstract

14561 Background: Colon cancer is second only to lung cancer in men and to breast carcinoma in women, for incidence and mortality in western countries .The higher incidence per age is observed between the sixth and seventieth decade, while 60% of the patients survive up to five years. The most important reason for the low percentage of recoveries is due to the fact that when the primary tumour is removed, a high number of patients have already developed micro-metastases, principally at liver. Therefore, methods for early screening are requested. Molecular markers have emerged as an important strategy to evaluate the individual susceptibility for cancer insorgence and for clinical cancer therapy. Recent studies have demonstrated an increase in clusterin expression in breast carcinoma suggesting a possible role of this protein in tumour progression. Clusterin is an heterodimeric (a and β chains) ubiquitous glycoprotein implicated in a large number of physiological processes and in the control of cellular proliferation. Despite the original hypothesis that clusterin is a marker for programmed cell death, several experiments and clinical studies have demonstrated conflicting findings on its role in tumors. Methods: We have studied clusterin isoforms expression in tumour progression, in particular in the adenoma-carcinoma sequence of colorectal cancer. Results: the observation of 35 samples of human intestinal mucosa, such as endoscopic biopsies and surgical specimens, demonstrated that the progression towards high grade and metastatic colon carcinoma leads to a pattern shift of clusterin isoforms production, the complete loss of the proapoptotic nuclear form and an over expression of cytoplasmic secreted form correlateting to a phenotype with high metastatic potential. Moreover we observed in tumor biopsies the release of clusterin in the crypts lumen. The ELISA immuno-dosage of clusterin demonstrated that the sclusterin overexpression in tumours correlates to a significant increase of clusterin in the serum and stools of patients affected by tumoural pathologies and in particular by colorectal cancer. Conclusions: These data suggests a new role of secreted clusterin as a new diagnostic circulating marker and a potential new therapeutic target. No significant financial relationships to disclose.