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Genetics Factors and Tumor Markers in Upper Urinary Tract-Urothelial Carcinoma

  • Mark Ferretti
  • John L. Phillips
Chapter

Abstract

The diagnosis of urothelial carcinoma of the upper urinary tract (UUT) may be more elusive than for UC of the bladder especially for low-stage, low-volume disease. Genetic markers may allow the diagnosis and possible prognosis of UUT-UC based on the very small tissue samples obtained through endoscopic biopsy. Families with UUT-UC are rare but point to distinct genetic features that may underlie sporadic cases such as mutations in the DNA mismatch repair (MMR) genes. MMR mutations are thought to lead to inability to repair DNA copy errors during replication causing microsatellite instability (MSI) and mutations in p53 or FGFR3. Cytology has low sensitivity in the diagnosis of low-stage UUT-UC, especially after post-cystectomy urinary diversion to bowel. Diagnostic yield may be improved by chromosomal enumeration tests (e.g., FISH), DNA assays (e.g., p53 status, methylation status, FXYD3 gene), and/or protein markers (e.g., ImmunoCyt, BTA Stat, Nuclear Matrix Protein 22 (NMP22), survivin, telomerase). Markers may also be used to identify patients who may be at risk of bladder recurrence after nephroureterectomy (e.g., expression of TP53 and E-cadherin). No single tumor marker appears to have enough specificity and sensitivity to obviate the need for careful endoscopic and imaging evaluation of the patient who may have UUT-UC. However, genetic markers continue to improve the ability to lateralize, diagnose, and predict failure after conservative or definitive management of a commonly aggressive neoplasm subtype.

Keywords

Upper urinary tract-urothelial carcinoma Genetics Mismatch repair (MMR) genes Fluorescent in situ hybridization (FISH) Microsatellite mutation analysis Lynch syndrome Molecular markers 

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of UrologyWestchester Medical Health Network/New York Medical CollegeValhallaUSA

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