Background and objectives: Dysregulation of TGF-β signaling plays multiple roles in cancer development and progression. In the canonical TGF-β pathway, TGF-β regulates the expression of hundreds of target genes via interaction with Smads, signal transducers and transcriptional modulators. We evaluated the association of TGF-β1, Smad2, and Smad4, the key components of canonical TGFβ pathway, with clinicopathologic characteristics of urothelial bladder cancer, and assessed their prognostic value in prediction of patients’ outcome. Materials and Methods: Immunohistochemical analysis of TGF-β1, Smad2, and Smad4 expression was performed on 404 urothelial bladder cancer samples, incorporated in tissue microarrays. Expression status was correlated with clinicopathological and follow-up data. The median follow-up was 61 months. Results: High expression of TGF-β1, Smad2, and Smad4 was detected in 68.1%, 31.7% and 45.2% of the tumors, respectively. TGF-β1 overexpression was significantly associated with high tumor grade, and advanced pathologic stage (p < 0.001, respectively). Conversely, high Smad2 and Smad4 expression was linked to low tumor grade (p = 0,003, p = 0.048, respectively), and low tumor stage (p < 0.001, p = 0.003, respectively). Smad2 showed an inverse correlation with variant morphology and divergent differentiation of urothelial tumors (p = 0.014). High TGF-β1 correlated directly, while Smad2 and Smad4 correlated inversely to cancer-specific death (p = 0.043, p = 0.003, and p = 0.022, respectively). There was a strong relationship between Smad2 and Smad4 expression (p < 0.001). Survival analyses showed that high Smad2 and Smad4 expression was associated with longer overall survival (p = 0.003, p = 0.034, respectively), while in multivariate regression analysis TGF-β1 manifested as an independent predictor of poor outcome. Conclusions: Unraveling the complex roles and significance of TGF-β signaling in urothelial bladder cancer might have important implications for therapy of this disease. Assessment of TGF-β pathway status in patients with urothelial bladder cancer may provide useful prognostic information, and identify patients that could have the most benefit from therapy targeting TGF-β signaling cascade.

Primary mediastinal large B-cell lymphoma has been recognised as a distinct entity with unique clinical, pathologic, and genetic features. According to WHO 2008 classification it is marked as a variant of diffuse large B-cell lymphoma but shares characteristics with classic Hodgkin lymphoma....

INTRODUCTION: Synchronous occurrence of lymphomas and other cancers, mostly carcinomas are well established. The most of cases describe chronic lymphocytic leukemia as the leading lymphoproliferative disease with tendency towards secondary malignancies development. Mantle cell lymphoma (MCL) has been described in only 2 cases to co-occur with prostate adenocarcinoma (PAC). We present a first case of synchronous occurrence of MCL and PAC in the same patient in Serbia. There are scarce data about the connection between MCL and urology cancers. CASE REPORT: 64-year-old male initially presented with fatigue, splenomegaly, and bycitopenia. The bone marrow biopsy specimen revealed extensive infiltration with MCL. During lymphoma staging procedure prostate enlargement (57mm) was accidentally found by multislice-computed tomography (MSCT). The prostate specific antigen (PSA) was elevated (52 ng/mL). Transrectal ultrasound (TRUS) biopsy revealed PAC. High Gleason score determined high-risk locally advanced PAC. The patient underwent treatment with chemotherapy and hormonotherapy due to the existence of double malignancies. CHOP (cyclophosphamide, doxorubicin, vincristine, prednison) was applied for MCL, and LH/RH agonist triptorelin for PAC. Partial response was obtained for MCL, and PAC was in stable condition. In 1.5-year observation period patient is still disease progression free for both of malignancies. CONCLUSION: This case point up that elderly male need careful observation during staging procedure for lymphoma. The literature data suggest that MCL patients have an increased risk for urologic malignancies development. However, the etiologic connection between these two entities, except male gender and older age, remains unclear.