The Lund Taxonomy for Bladder Cancer Classification - From Gene Expression Clustering to Cancer Cell Molecular Phenotypes, and Back Again.

Treatment of bladder cancer patients depends on precise diagnosis. Molecular subtyping by gene expression profiling may contribute substantially to subclassification of bladder cancer. Several classification systems have been presented. Most of these base their classification on whole biopsy features, and molecular subtypes are therefore often defined by a combination of features from the cancer cells as well as infiltrating non-cancer cells. This makes the link to what is seen at the cancer cell level unclear. The aim of the Lund Taxonomy has been to align gene expression level classification with immunohistochemical classification to identify cancer cell phenotypes independent of infiltration and proliferation. A systematic approach was used, in which gene expression clusters were validated and adjusted by immunohistochemistry using markers expressed only by the cancer cells. In the present review the rationale for defining molecular subtypes is provided, as well as a step-by-step description of the development of the Lund Taxonomy with motivations for each modification and extension. As the cancer cell phenotype defined by gene expression profiling corresponds with immunohistochemistry of cancer cells, the Lund Taxonomy represents a harmonization of the gene expression and immunohistochemical levels. Furthermore, the classification system is independent of pathological stage and is thus applicable to all urothelial carcinomas. A unified classification system relevant for both the molecular biologist and pathologist will facilitate systematization of current treatment practices, as well as the development of new treatments. This article is protected by copyright. All rights reserved.