Editorial Comment to CD74 expression is increased in high‐grade, invasive urothelial carcinoma of the bladder
2012-08-31

Despite bladder cancer being considered to be an immunogenic tumor, as underlined by its potential response to intravesical bacillus Calmette–Guérin immunotherapy in early invasive stages,1 the role of the immune system in invasive bladder cancer for prognosis and treatment has not been fully acknowledged in the uro-oncological community so far. The authors of the present study are to be congratulated for carrying out a dedicated correlation analysis on CD74 expression in bladder cancer tissues as a potential rationale for a targeted therapy.2 CD74 is a major histocompatibility complex class II protein on immune cells, which serves as a receptor for the macrophage migration inhibitor factor. Interestingly, in this study, high CD74 expression correlated inversely with the presence of tumor-infiltrating inflammatory cells, and was positively associated with high-grade and high-stage cancers. These results suggest that effective bladder cancer control necessitates an intact immune system and underpin, once more, the critical role of the immune system for preventing tumor progression in invasive bladder cancer. In the past decade, enormous efforts have been undertaken to evaluate the prognostic role of molecular markers in invasive bladder, focusing mainly on well-known downstream signaling pathways; that is, the p53, pTEN and retinoblastoma pathway.3 However, tissue-based marker expression analyses inherit the disadvantage that their measurement does not permit real-time assessment of treatment response, which could be an important factor for monitoring treatment response in patients undergoing neoadjuvant chemotherapy. By contrast, an increasing number of studies recently reported on the prognostic significance of immunological serum-based parameters as potential predictors of survival, as serum-C-reactive protein, thrombocytosis and neutrophile-to-lymphocyte ratio, which can be assessed easily in daily clinical routine at low cost.4-6 Nonetheless, while in other malignancies molecular markers have found their way into clinical practice; for example, CA125 in ovarian cancer,7 there is no marker in invasive bladder cancer that has been recommended for routine clinical use to date. This is due to the fact that only a few studies have investigated the exact increase in the predictive accuracy of a putative marker within basic models encompassing prognostic pathological parameters.3 Importantly, in most tissue-based marker studies, a prognostic benefit was only found when a multimarker panel was added to a basic model.3 This underscores the fact that tumor progression in bladder cancer is associated with dysregulation of several molecular pathways. In turn, it means that it is unlikely that researchers will find a single marker solely responsible for tumor progression in bladder cancer. Thus, it seems unsurprising that in the present study multivariable analysis did not find CD74 to be independently associated when compared with well-established clinicopathological parameters of survival.2 Therefore, it is necessary to further investigate its up- and downstream molecular pathway in order to provide a profound rationale for the use of a CD74 targeted approach in invasive bladder cancer within clinical trials. None declared.