Myopodin methylation is a prognostic biomarker and predicts antiangiogenic response in advanced kidney cancer.

Myopodin is a cytoskeleton protein that shuttles to the nucleus depending on the cellular differentiation and stress. It has shown tumor suppressor functions. Myopodin methylation status was useful for staging bladder and colon tumors and predicting clinical outcome. To our knowledge, myopodin has not been tested in kidney cancer to date. The purpose of this study was to evaluate whether myopodin methylation status could be clinically useful in renal cancer (1) as a prognostic biomarker and 2) as a predictive factor of response to antiangiogenic therapy in patients with metastatic disease. Methylation-specific polymerase chain reactions (MS-PCR) were used to evaluate myopodin methylation in 88 kidney tumors. These belonged to patients with localized disease and no evidence of disease during follow-up (n = 25) (group 1), and 63 patients under antiangiogenic therapy (sunitinib, sorafenib, pazopanib, and temsirolimus), from which group 2 had non-metastatic disease at diagnosis (n = 32), and group 3 showed metastatic disease at diagnosis (n = 31). Univariate and multivariate Cox analyses were utilized to assess outcome and response to antiangiogenic agents taking progression, disease-specific survival, and overall survival as clinical endpoints. Myopodin was methylated in 50 out of the 88 kidney tumors (56.8 %). Among the 88 cases analyzed, 10 of them recurred (11.4 %), 51 progressed (57.9 %), and 40 died of disease (45.4 %). Myopodin methylation status correlated to MSKCC Risk score (p = 0.050) and the presence of distant metastasis (p = 0.039). Taking all patients, an unmethylated myopodin identified patients with shorter progression-free survival, disease-specific survival, and overall survival. Using also in univariate and multivariate models, an unmethylated myopodin predicted response to antiangiogenic therapy (groups 2 and 3) using progression-free survival, disease-specific, and overall survival as clinical endpoints. Myopodin was revealed hypermethylated in kidney cancer. Myopodin methylation status identified which patients showed a more aggressive clinical behavior and predicted antiangiogenic response. These observations support the clinical utility of an unmethylated myopodin as a prognostic and predictive biomarker in kidney cancer.

The neuroendocrine component in bladder tumors.

Neoplastic urothelium has the capacity to display enormous plasticity and divergent differentiation. Neuroendocrine tumors arise as a result of such capacity. Neuroendocrine tumors of the bladder represent a limited number of neoplasms characterized by neuroendocrine hormone secretion and a poor outcome. These tumors can be displayed as pure neuroendocrine neoplasms or more frequently as a neuroendocrine counterpart mixed with classical urothelial bladder cell carcinomas, adenocarcinoma, sarcomatoid carcinoma or mixtures of these components. Their heterogeneous character and clinical aggressiveness remain a challenge for clinical, pathological diagnosis and for therapy selection. Several types have been described, although small cell carcinoma represents the major subgroup of neuroendocrine tumors as compared to large cell carcinoma and carcinoid subtypes. In this review, epidemiology, presentation, macroscopic and microscopic features, and clinical prognostic and therapeutic implications of the major subgroups are described. Special focus is given to discuss how immunohistochemistry protein patterns and laboratory determinations may aid to characterize this type of tumors and to improve the clinical management of this highly aggressive type of bladder cancer patients.