Tetraspanin CD63 independently predicts poor prognosis in colorectal cancer

CD63, a member of the tetraspanin family, is expressed in endosomes and enriched in exosomes. Tetraspanins participate in a variety of physiological processes, including cellular differentiation, cell-cell fusion, and cell migration. CD63 reportedly carries both protumorigenic and tumor suppressor properties, and appears to be upregulated in breast cancer, astrocytoma, and melanoma. Yet, the effect of CD63 on cancer prognosis remains unclear, and no previous reports examined it in colorectal cancer (CRC). Identifying novel biomarkers will allow us to better differentiate patients with an increased risk of recurrence and who might benefit from adjuvant therapy. We applied immunohistochemistry with antibodies to human CD63 on 620 consecutive CRC patients treated at the Helsinki University Hospital. We evaluated the associations between CD63 expression and clinicopathological parameters and patient prognosis. We found that CD63 expression associated with an advanced stage, poor differentiation, and mucinous histology. We found no association between CD63 expression and age, sex or tumor location. CD63 expression predicted an unfavorable prognosis in CRC (p=0.00001, log-rank test) and in a subgroup of patients with metastasized CRC (p=0.011). Cox's multivariate analysis identified CD63 as an independent factor predicting an unfavorable prognosis in CRC and in the subgroup with metastasized disease. We show for the first time that CD63 immunohistochemistry expression represents an independent marker of an unfavorable prognosis in CRC and associates with unfavorable clinicopathological parameters. Our results support the hypothesis that a higher tissue expression of CD63 in CRC, indicating an epithelial-to-mesenchymal transition (EMT)-associated secretory phenotype, associated with an adverse outcome.