Molecular and histological markers in urothelial carcinomas of the upper urinary tract

Abstract

Urothelial cell carcinomas (UCCs) are one of the most common types of malignancies. Recently, different mechanisms of carcinogenesis, as well as discrepancies in the natural history of urothelial cancers of the bladder and of the upper urinary tract (UUT), have been identified. As a result several teams have focused on specific markers in UUT-UCCs, a very rare type of cancer. This review gives a brief overview on the current markers of interest. Microsatellite instabilities (MSI) are independent molecular makers for prognosis. In addition, MSI can help detect a germline mutation and therefore allows for the detection of possible hereditary cancers. The loss of proteins of the mismatch repair system can also facilitate the detection of a germline mutation but should be followed by DNA sequencing. Epithelial cadherin has been shown to be an independent marker of prognosis, as well as hypoxia-inducible factor-1alpha (HIF-1alpha) and telomerase RNA component. Furthermore HIF-1alpha is significantly associated with the grade and pattern of growth and the telomerase RNA component could possibly also be used in diagnosis. The active form of the L-type amino acid transporter 1 (LAT1) was a significant prognostic marker in univariate analysis only. There are contrasting studies on the significances of p27 and Ki-67 as prognostic markers in UUT-UCCs. MET is a factor that correlates with vascular invasion of invasive cancer and bcl-2 oncoprotein correlates with stage. The ongoing identification of these markers might help to find specific treatments tailored to the molecular pattern of each tumour. Therefore a subgroup of patients with a higher risk of recurrence could be identified as well as patients that could benefit from minimal invasive surgery.