Breast carcinoma in Egyptian women is a biologically more aggressive disease than those diagnosed in Western women, although a substantial number of cases are hormone responsive. G protein-coupled receptor-30 (GPR30), a seven transmembrane domain protein, is currently recognized as an estrogen receptor. This study aimed at evaluating the expression of GPR30 in breast carcinomas of Egyptian patients and its association with clinicopathologic parameters and immunohistochemical subtypes of breast carcinoma. Immunohistochemical staining for GPR30 was applied on 51 archival formalin-fixed paraffin-embedded cases of invasive ductal carcinoma. Staining was assessed using a semiquantitative scoring system taking staining intensity and extent into consideration. GPR30 was observed in 33/51 (65%) of invasive ductal carcinoma cases. GPR30 was significantly associated with larger tumor size (p = 0.009), increased number of positive lymph nodes (p = 0.04), definite lymph-vascular invasion (LVI) (p = 0.002), peri-nodal invasion (p = 0.02), and the presence of coagulative tumor cell necrosis (p = 0.02). Moreover, a significant association between positive GPR30 expression and ER positivity (p = 0.02), as well as HER2/neu positivity (p = 0.03), were also observed. Most of the luminal A and B subtypes were GPR30 positive; however, all the triple negative cases were GPR30 negative (p = 0.010). GPR30 might contribute to the aggressive behavior of Egyptian breast carcinoma. Therefore, it could be useful in the therapeutic decision making in breast cancer patients.
Objective: Diffuse Large B Cell Lymphoma (DLBCL) is a heterogeneous group of tumors with different biological and clinical characteristics that have diverse clinical outcomes and response to therapy. Stromal-1 signature of tumor microenvironment of DLBCL represents extracellular matrix deposition and histiocytic infiltrate, whereas stromal-2 represents angiogenesis that could affect tumor progression.Methods: The aim of the present study is to assess the significance of stromal-1 signature using SPARC-1 and stromal-2 signature using CD31 expression and then finally to construct biologic prognostic model (BPM) in 60 cases of DLBCL via immunohistochemistry.Results: Microvessel density (P<0.05) and SPARC percentage of expression (P<0.001) were higher in DLBCL, including germinal and nongerminal cases, compared with reactive follicular hyperplasia. High microvessel density was significantly associated with splenic involvement (P=0.008), high mitotic count (P=0.045), and presence of capsular invasion (P=0.035). Percentage of SPARC expression was significantly associated with splenic involvement (P=0.03). Constructing BPM showed that 42 cases (70%) were of low biologic score (0–1) and 18 cases (30%) were of high biologic score (2–3). Low BPM cases showed less probability for splenic involvement (P=0.04) and a higher rate of complete response to therapy compared with high score cases (P=0.08). Conclusions: The DLBCL microenvironment could modulate tumor progression behavior since angiogenesis and SPARC positive stromal cells promote dissemination by association with spleen involvement and capsular invasion. Biologic prognostic models, including modified BPM, which considered cell origin of DLBCL and stromal signature pathways, could determine DLBCL progression and response to therapy.
Ephrin receptors and ephrin ligands constitute one of the largest groups of tyrosine kinases. The division of ephrin receptors into type A or type B is determined by their ligand-binding specificities. Ephrin A4 as a ligand has a broad capacity to bind and stimulate different subtypes of ephrin A receptors. Little is known about the role of ephrins generally and ephrin A4 particularly in osteosarcoma. Ephrin A4 was immunohistochemically assessed on archival material from 46 primary osteosarcoma cases, 10 metastatic pulmonary lesions and 20 normal control bone specimens. Ephrin A4 was expressed in 100% of normal bone specimens, in 84.4% of primary osteosarcoma cases and in all metastatic pulmonary lesions. Cytoplasmic and nucleocytoplasmic patterns of ephrin A4 immunoreactivity were observed, with the predominance of the latter pattern in normal bone (100%), and in 43.5% of primary osteosarcoma cases, which showed a higher intensity of expression compared with normal bone (p<0.05). The cytoplasmic pattern is the only staining pattern seen in metastatic cases, which may suggest its role in enhancement of invasion and metastasis. The differences in the distribution of the two patterns of ephrin A4 may indicate a different biological activity of this molecule depending on its localization. The nuclear localization of ephrin A4 requires further investigation to clarify the mechanism and the significance of the nuclear trafficking of ephrin A4.
EBV infection is frequent in PELHN in Egypt. Possible pathogenic mechanisms involve deregulation of p53 and enhanced proliferation (as detected by high Ki67 index). The presence of del-LMP1 variants, p53 overexpression and advanced disease stage are poor prognostic factors associated with reduced survival and poor response to therapy.
Tumor-associated macrophages (TAMs) and dendritic cells (DCs) may play a role in tumor progression as a part of the tumor microenvironment in many neoplasms, including those in Hodgkin's lymphoma. The current study investigated the relationship between the presence and density of macrophages and dendritic cells in the background of classic Hodgkin's lymphoma (CHL) and different clinicopathological parameters, including survival and response to therapy. CD68 and CD1a immunohistochemical staining were used to detect and highlight macrophages and dendritic cells, respectively, in 61 cases of CHL. CD68 was expressed in all studied cases, with no significant association with the studied parameters. In total, 54.1% (33/61) of cases showed CD1a expression. High CD1a expression (>7%) was associated with localized lymphadenopathy (p=0.01), early stage (p=0.005), and good revised international prognostic index (R-IPI) (p=0.07). Hodgkin's lymphoma cases that showed high CD68 and low CD1a were associated with adverse prognostic parameters such as advanced stage (p=0.03) and generalized lymphadenopathy (p=0.05). Old age (>60 years) (P=0.005), poor R-IPI (P=0.010), and negative CD1a expression (P=0.045) were significantly associated with poor outcome. Finally, our study demonstrated the importance of the presence and density of DCs in determining progression and prognosis in CHL. A certain interaction between TAMs and DCs may affect the progression of CHL. Further investigation is required to clarify whether TAMs release certain factors that decrease the number or function of DCs.
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