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Obesity-related glomerulopathy (ORG) is a secondary form of focal segmental glomerulosclerosis (FSGS) occurring in obese patients with a body-mass index higher than 30 kg/m(2). It is typically manifested by nephrotic-range proteinuria without full nephrotic syndrome, and progressive renal insufficiency. Characteristic morphologic features include the consistent presence of glomerulomegaly, predominance of perihilar variant of FSGS, and the relatively mild fusion of visceral epithelial cell foot processes. The concept of podocyte depletion as a driver of the glomerular scarring in obesity-associated FSGS is well documented. The underlying mechanisms are likely to be related in part to the oxidative stress and the impairment of the integrity of the slit diaphragm and cell adhesion resulting mainly from angiotensin II and transforming growth factor-β. These proapoptotic cytokines are upregulated in obesity in response to insulin resistance, compensatory hyperinsulinemia and glomerular hyperfiltration-hypertension mediated mechanical stress. This review is designed to discuss the clinicopathologic features of obesity-associated FSGS, with a focus on the podocyte injury, which is involved in the onset and progression of the glomerulosclerotic process. Ultrastructural glomerular lesions are documented.

PurposeThe aim of this study was to evaluate the Immunoscore (IS) methodology as a prognostic marker of colorectal adenocarcinoma in Tunisian population. Tumor blocks were retrospectively collected from 106 patients with sporadic colorectal cancer.MethodsImmunohistochemical staining and images analysis software were used to quantify the density of CD3+ and CD8+ tumor-infiltrating lymphocytes in the center of the tumor and invasive margin.ResultsThe density of CD3+ and CD8+ was significantly associated with 5-year overall survival (P=0.001 and P=0.00098, respectively) and 5-year disease-free survival (P=0.0006 and P=0.0056, respectively). The earlier stage and the absence of vascular emboli showed a significant association with IS analysis. Cox multivariate regression analysis revealed that Immunoscore (from I0 to I4) was more significantly correlated with overall survival (P=0.00011) and disease-free survival (P=0.0008) than Tumor-Node-Metastasis (TNM) staging (P=0.057 and P=0.039, respectively). Patients with low IS were associated with inferior disease-free survival and overall survival, contrary to patients with high IS.ConclusionThis is the first study which evaluated the prognostic value of IS methodology in colorectal cancer in African and Arabic population. The IS methodology carries out in this study allows to estimate the risk of relapse in patients with colorectal cancer. Overall, our results support the implementation of the consensus Immunoscore as a new component for the classification of cancer, designated TNM-Immune.

Epithelial odontogenic tumors are rare jaw pathologies that raise clinical diagnosis and prognosis dilemmas notably between ameloblastomas and clear cell odontogenic carcinomas (CCOCs). In line with previous studies, the molecular determinants of tooth development—amelogenin, Msx1, Msx2, Dlx2, Dlx3, Bmp2, and Bmp4—were analyzed by RT-PCR, ISH, and immunolabeling in 12 recurrent ameloblastomas and in one case of CCOC. Although Msx1 expression imitates normal cell differentiation in these tumors, other genes showed a distinct pattern depending on the type of tumor and the tissue involved. In benign ameloblastomas, ISH localized Dlx3 transcripts and inconstantly detected Msx2 transcripts in epithelial cells. In the CCOC, ISH established a lack of both Dlx3 and Msx2 transcripts but allowed identification of the antisense transcript of Msx1, which imitates the same scheme of distribution between mesenchyme and epithelium as in the cup stage of tooth development. Furthermore, while exploring the expression pattern of signal molecules by RT-PCR, Bmp2 was shown to be completely inactivated in the CCOC and irregularly noticeable in ameloblastomas. Bmp4 was always expressed in all the tumors. Based on the established roles of Msx and Dlx transcription factors in dental cell fates, these data suggest that their altered expression is a proposed trail to explain the genesis and/or the progression of odontogenic tumors.

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