Upper urinary tract urothelial cell carcinomas and other urological malignancies involved in the hereditary nonpolyposis colorectal cancer (lynch syndrome) tumor spectrum

Eur Urol. 2008 Dec;54(6):1226-36. doi: 10.1016/j.eururo.2008.08.008. Epub 2008 Aug 12.

Abstract

Context: The data describing the urologic extracolonic cancers associated with hereditary nonpolyposis colorectal cancer (HNPCC) are variable.

Objective: Provide an update about the current urologic tumor spectrum in HNPCC.

Evidence acquisition: Data on HNPCC extracolonic tumor spectrum published in the literature were analysed using MEDLINE with emphasis on urological malignancies, upper tract tumors, clinical criteria, genetic diagnosis and counselling.

Evidence synthesis: HNPCC is a form of colorectal cancer with a dominant autosomal mode of inheritance. HNPCC is caused by germ-line mutations affecting one or several mismatch repair genes. Cancers other than colorectal cancer are sometimes associated with HNPCC. These include specific urological malignancies, most notably tumors of the upper urinary tract, which have been reported to occur at a rate x22 higher than the general population. Upper urinary tract tumors rank third (5%) after colon (63%) and endometrial (9%) cancer within the group of HNPCC related tumors. Prostate cancer and testicular germ cell tumors are rarely associated. Due to lack of appreciation of such hereditary associations, some inherited cancers are still misclassified as sporadic and their incidence is underestimated. The biological tests requested in suspected cases of HNPCC are: microsatellite instability (MSI) analysis, immunohistochemistry and DNA sequencing. When gene mutations are detected, the patient and their family will benefit from a multidisciplinary management approach. The presence of other HNPCC-associated cancers is sought and close monitoring of patients is undertaken. Genetic counselling is provided to the patient's family.

Conclusions: The recognized urologic tumor spectrum in HNPCC includes upper tract tumors. However, in order not to overlook a hereditary cancer, urologists should be aware of the possible urological malignancies associated with HNPCC (i.e., prostate and testicular carcinomas) and evaluate appropriately anyone they feel are at high risk of underlying HNPCC based on set clinical criteria.

Publication types

  • Review

MeSH terms

  • Carcinoma, Transitional Cell* / diagnosis
  • Carcinoma, Transitional Cell* / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / diagnosis
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / genetics
  • Humans
  • Kidney Neoplasms / diagnosis
  • Kidney Neoplasms / genetics
  • Neoplasms, Multiple Primary* / diagnosis
  • Neoplasms, Multiple Primary* / genetics
  • Ureteral Neoplasms / diagnosis
  • Ureteral Neoplasms / genetics
  • Urologic Neoplasms* / diagnosis
  • Urologic Neoplasms* / genetics