Prognostic significance of annexin A2 and tumor associated macrophages (TAMs) in metastatic renal cell carcinoma and their relation to Sunitinib resistance.

Sunitinib, an antiangiogenic tyrosine kinase inhibitor, is the main treatment for metastatic renal cell carcinoma (mRCC). Development of resistance is a major obstacle against therapy success. The aim of this study was to assess annexin A2 and CD163+ tumor associated macrophages (TAMs) immunohistochemical expression in 50 mRCC cases as regard to patients' prognosis and Sunitinib response. Also, to assess the correlation between annexin A2 and TAMs expression. High annexin A2 expression and TAMs density were associated with serum calcium level (P = 0.024 and 0.037, respectively), larger tumor size (P < 0.001), high tumor grade (P = 0.014 and <0.001, respectively), and the presence of tumor necrosis (P < 0.001). High annexin A2 and TAMs expressions were related to shorter patients' overall survival (P = 0.009 and 0.001, respectively) and progression-free survival (P = 0.003 and 0.001, respectively). Annexin A2 was correlated with TAMs density (r = 0.890). Annexin A2 and TAMs are associated with poor prognostic parameters in mRCC patients, including high nuclear grade, increased tumor size, and the presence of tumor necrosis, together with shorter patients' survivals and poor response to Sunitinib. Annexin A2 expression is correlated with TAMs density suggesting immunomodulatory role of annexin A2.

Evaluation of the prognostic significance of receptor tyrosine kinase-like orphan receptor 1 (ROR1) in lung carcinoma and its relation to lymphangiogenesis and epithelial mesenchymal transition.

Exploring the carcinogenic mechanisms of lung carcinoma helps to discover novel prognostic biomarkers and develop new therapeutic options to improve patient's survival. Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1), a transmembrane protein, contributes to cancer progression and metastasis; via stimulation of epithelial mesenchymal transition (EMT) and promotion of angiogenesis. This makes ROR1 an important target for tumor therapy. This study aimed to evaluate expression of ROR1, E-cadherin (a marker of EMT), and D2-40 (a marker of lymphangiogenesis) in lung carcinoma and associate their expressions with the available clinicopathological parameters and patients' survival. Immunohistochemical staining using ROR1, E-cadherin, and D2-40 was performed for 78 cases of lung carcinoma. Kaplan-Meier survival curves and Cox-regression analysis were done. High ROR1 expression was detected in 46.2% of cases. Significant relations were found between high ROR1 expression and larger tumor size (P < 0.001), poorly differentiated tumors (P = 0.001), advanced tumor stages (P < 0.001), positive lymph nodal status (P < 0.001), decreased E-cadherin expression (P < 0.001), and high lymphovascular density (LVD) (P < 0.001). Patients' progression free survival (PFS) and overall survival (OS) were shorter with high ROR1 expression. High ROR1 expression, high LVD, large tumor size, and adenocarcinoma histopathological type were independent risk factors for OS in lung carcinoma patients. High ROR1 expression is associated with poor prognostic parameters in lung carcinoma patients including higher grade, advanced stages, high LVD, epithelial mesenchymal transition, as well as decreased PFS and OS.

Medulloblastoma: clinicopathological parameters, risk stratification, and survival analysis of immunohistochemically validated molecular subgroups.

BACKGROUND: Medulloblastoma (MB) is a heterogeneous disease, displaying distinct genetic profiles with specific molecular subgroups. This study aimed to validate MB molecular subgrouping using surrogate immunohistochemistry and associate molecular subgroups, histopathological types, and available clinicopathological parameters with overall survival (OS) and progression-free survival (PFS) of MB patients. This study included 40 MBs; immunohistochemical staining, using ß-catenin and GRB2-Associated Binding Protein 1 (GAB1) antibodies, was used to classify MB cases into wingless signaling activated (WNT), sonic hedgehog (SHH), and non-WNT/SHH molecular subgroups. Nuclear morphometric analysis (for assessment of degree of anaplasia) and Kaplan-Meier survival curves were done. RESULTS: MB cases were classified into WNT (10%), SHH (30%), and non-WNT/SHH (60%) subgroups. Histopathological types differed significantly according to tumor location (p< 0.001), degree of anaplasia (p = 0.014), molecular subgroups (p < 0.001), and risk stratification (p = 0.008). Molecular subgroups differed significantly in age distribution (p = 0.031), tumor location (p< 0.001), histopathological variants (p < 0.001), and risk stratification (p < 0.001). OS was 77.5% and 50% after 1 and 2 years, while PFS was 65% and 27.5% after 1 and 2 years, respectively. OS and PFS were associated significantly with histopathological variants (p < 0.001 and 0.001), molecular subgroups (p = 0.012 and 0.005), and risk stratification (p < 0.001 and < 0.001), respectively. CONCLUSIONS: Medulloblastoma classification based on molecular subgroups, together with clinicopathological indicators, mainly histopathological types; accurately risk stratifies MB patients and predicts their survival.