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urothelial carcinoma

Thursday 10 September 2009

transitional cell carcinomas of the urinary tract, urothelial carcinoma, UCC, urothelial cell carcinoma

Definition: Urothelial cell carcinomas (UCC), including bladder cancer and upper urinary tract cancer, are the second most common malignancy of the urogenital tract after prostate cancer.

Digital cases - Digital slides

- UI:513 : Urothelial carcinoma (transitional cell carcinoma) in-situ
- UI:363 : Urothelial carcinoma grade 1 (transitional cell carcinoma grade 1)

Types

- low-grade urothelial carcinoma (LGUC )
- high-grade urothelial carcinoma (HGUC / aggressive urothelial carcinoma)

  • usual-type high-grade urothelial carcinoma.
  • plasmacytoid urothelial carcinoma
  • signet ring cell urothelial carcinoma
  • micropapillary urothelial carcinoma

- large nested variant of urothelial carcinoma

Localization

- urothelial cell carcinoma of the upper urinary
- urothelial cell carcinoma of the bladder

Differential diagnosis

- High-grade lesions can have denuded epithelium due to discohesion the neoplastic cells.

  • Thorough examination of any clinging cells for atypia of should be performed.
  • Correlation with clinical results

- Reactive changes are difficult to distinguish from urothelial dysplasia.

  • Immunohistochemistry for CK20, p53, CD44, and/or HER2/neu can be performed.

- Morphologic heterogeneity is seen within a single tumor.

  • Quantify and/or describe all morphologies seen, including any variant morphologies, such as micropapillary, and correlate with clinical information and cystoscopic findings.

- Cautery artifact or tangential sectioning

  • Highlighting neoplastic cells with a pankeratin and smooth muscle cells with desmin or smoothelin can aid in evaluation and staging of invasion.

Microsatellite instabilities (MSI)

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.

DNA methylation

DNA methylation is an important epigenetic mechanism of gene regulation and plays essential roles in tumour initiation and progression. Currently, aberrant promoter hypermethylation has been investigated in specific genes, i.e. tumour-suppressor genes, proto-oncogenes, genes involved in cell adhesion, and genes of cell cycle regulation. E-cadherin has been shown to be an independent marker of prognosis.

Other genes, e.g. APC, RASSF1a, TNFRSF25, EDNRB, and p14, are implicated in tumour progression. IGFBP3 and APAF-1 are independent markers of recurrence. APAF-1 is also correlated with tumour stage and grade. In urine, hypermethylation of DAPK, RARbeta, E-cadherin and p16 has been shown to have a good sensitivity and specificity for bladder cancer detection.

Several studies found that analysis of hypermethylation using a panel of tumour-suppressor genes yielded superior results to cytology in the detection of bladder cancer and its progression.

References

- Molecular and histological markers in urothelial carcinomas of the upper urinary tract. Eltz S, Comperat E, Cussenot O, Rouprêt M. BJU Int. 2008 Aug 5;102(5):532-5. PMID: 18384628

- Interest of methylated genes as biomarkers in urothelial cell carcinomas of the urinary tract. Phé V, Cussenot O, Rouprêt M. BJU Int. 2009 Jun 12. PMID: 19522860