There are 2 critical components which influence tumor heterogeneity and include tumor microenvironment and sampling purity. The latter may lead to non-intrinsic molecular subtypes. In Lund, they noted high correlation between mRNA and immunohistochemistry (IHC) data from different tumor parts. For example, using central sampling of Lund 2002 and peripheral sampling of Lund 2017 they showed high correlation with similar results.
Tumor cell intrinsic subtypes can occur in the same tumor. In the Lund, cohort they have found approximately 50% of patients may have different intrinsic subtypes within the same tumor. However, these results only show this happens and does not describe the prevalence due to patients sampled and larger numbers needed. Using tissue microarrays, they defined heterogeneity between cores/within cores from the same tumor. However, only 1/3 differed in one of the 11 markers with others having even lower frequency.
In summary, intra-tumor heterogeneity does influence the molecular classification of bladder cancer. Tumor cell intrinsic subytpes are usually stable in repeat sampling, can co-occur in invasive bladder cancer and usually involve the basal/squamous subtype. Data are preliminary and further larger analyses are needed to understand the prevalence and validation studies to understand the impact on molecular classification.
Presented by: Gottfrid Sjödahl, University of Lund, Lund, Sweden
Written by: Stephen B. Williams, M.D., Associate Professor, Division of Urology, The University of Texas Medical Branch, Galveston, TX. and Ashish M. Kamat, M.D. Professor, Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX at the 16th Annual Meeting of the International Bladder Cancer Network (IBCN) October 11-13, 2018 - the Inntel Hotels Rotterdam Centre, Rotterdam, The Netherlands