Histology and histopathology Vol.34, nº6 (2019)
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- PublicationOpen AccessSTIM promotes the epithelial-mesenchymal transition of podocytes through regulation of FcγRII activity in diabetic nephropathy(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Jin, Juan; Ye, Meiyu; Hu, Kang; Gong, Jianguang; He, QiangBackground. Diabetic nephropathy (DN) is a serious complication in diabetic patients and has been considered as the main cause of end-stage renal disease. However, there are no studies on the role of stromal interaction molecule (STIM) and its two subtypes, STIM1 and STIM2, in the epithelial-to-mesenchymal transition (EMT) of podocytes induced by diabetic kidney disease (DKD). The present study suggests for the first time that STIM inhibition decreases DKDinduced EMT. Methods. All DKD patients were diagnosed based on renal biopsies carried out at the Department of Nephrology, Zhejiang Provincial People’s Hospital and selected using the Mayo Clinic/Renal Pathology Society Consensus Report on Pathologic Classification, Diagnosis, and Reporting of GN. Images were taken and the number of positive puncta in cells was analyzed using software equipped for immunofluorescence microscopy. STIM1, STIM2, FcγRIIa, FcγRIIb, Nephrin, CTGF, and α-SMA protein levels were detected by Western blotting analysis using the corresponding antibodies. The viability of cells was measured using CCK-8 assays. Absorbance at 450 nm was measured with a Multiskan FC Microplate Reader (Thermo Scientific, USA) and the results were normalized to those of untreated cells. All statistical analyses were performed using SPSS 19.0 software (Stanford University, Stanford, CA, USA). Results. A total of 30 DKD patients and 30 control patients were enrolled in the study. We found that the level of urine protein in patients and db/db diabetic mice is higher than control group and the levels of STIM1 and 2 significantly increased in DKD groups. We also demonstrated that STIM is upregulated during DKD injury. Next, we discovered that DKD-induced podocyte EMT is related to STIM overexpression in vivo and in vitro. Further research demonstrated that STIM siRNA reverses podocytes from DKD-induced injury and EMT and reverses FcγRII activity in HG-treated podocytes. Conclusion. Our study suggests that STIM and FcγRII play an essential role in the regulation of DKDinduced podocyte EMT. STIM is an essential component of FcγR activation and inhibition of STIM-mediated signaling pathway might be a new strategy to treat IgGdependent renal diseases.
- PublicationOpen AccessCorrelation of securin and Ki67 in invasive breast carcinoma(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Mamdouh Talaat, Iman; Akram Hamoudi, Rifat; Mahmoud Yakout, Nada; Youssef Oweiss, Nagwa; Mohammed Omar, AbbasAims. To identify the role of securin (PTTG) as a prognostic marker in invasive breast carcinoma and its possible relation to ki67 and to evaluate the use of ImmunoRatio® as a tool for calculating ki67 and securin labelling indices. Methods. Securin and ki67 immunohistochemical staining were performed on tissue microarray sections representative of 118 patients diagnosed with invasive breast carcinoma from 2005 to 2011. Assessment of immunohistochemical staining was carried out using both visual counting and ImmunoRatio®. The 118 cases were categorized into 2 groups according to their clinical outcome; the first group (G1) (n=77) comprised patients who were diseasefree while the second group (G2) (n=41) included patients who developed either recurrence and/or metastasis at the end of 24 months follow-up duration. Results. Both securin and ki67 labelling indices (LIs) obtained by visual counting were significantly higher in G2, while only securin LIs acquired by ImmunoRatio® were significantly higher in G2. Securin assessment by visual counting was the most accurate (AUC=0.775) in identifying patients who will likely suffer from recurrence and/or distant metastasis. Pearson correlation showed r=0.638, p<0.001 for Ki67 and r=0.671, p<0.001 for securin. Linear regression analysis showed a significant correlation between ki67 and securin, B=1.75, p<0.001. Conclusion. The present results suggest that securin may add to the prognostic value of ki67 in highlighting intra-tumoural heterogeneity in invasive breast carcinoma patients with poor clinical outcome. In addition, the study showed that since securin has a visual counting cutoff with more than 1%, making it easier to use as a breast cancer biomarker in conjunction with ki67 to predict the outcome of the cases more accurately than using only ki67. However, a multivariate analysis on a larger cohort of patients is mandatory to test its potential prognostic value.
- PublicationOpen AccessCytokeratin expression profiles of canine epithelial tissues(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Rickmeyer, Tina; Jäger, Kathrin; Schöniger, Sandra; Schoon, H.-A.Cytokeratins (CKs) are intermediate filaments of epithelial cells. In humans, different types of epithelia as well as their neoplasms show distinct CK expression profiles. The aim of this study was to establish a panel of CKs for the identification of specialized canine epithelia that can be integrated in a routine diagnostic setting. Immunohistochemistry was performed on 42 formalinfixed paraffin-embedded (FFPE) canine unaltered tissues including all epithelial tissues by using an antibody panel detecting CKs 7, 8, 13, 14, 17, 19 and 20 and the pancytokeratin marker AE1/AE3. Using this antibody panel, a differentiation scheme for the identification of canine tissues was developed. This allowed the identification of 23 out of the 42 examined canine tissues and the distinction of 9 groups of specialized epithelia. The statistical validation revealed high variations in the immunoreactivity for CKs 7, 8, 14, 17 and 20 between the donor dogs. The antibody detecting CK 7 (OV-TL 12/13) showed a decrease in immunostaining after a fixation time of 3 and 4 days. To the best of the authors’ knowledge this is the first study that characterizes all canine epithelial tissues for their expression of CKs 7, 8, 13, 14, 17, 19 and 20 and the pancytokeratin marker AE1/AE3. Results of this study are an important prerequisite for comparative histology and for the investigation into similarities/differences of the cytokeratin expression between normal and neoplastic epithelia. Since this study was performed on FFPE tissue, it can be included in the workflow of a routine diagnostic laboratory.
- PublicationOpen AccessEpstein - Barr virus (EBV) association with plasma cell neoplasms(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Nael, Ali; Wu, William W.; Siddiqi, Imran; Zhao, Xiaohui; Kahlon, Kanwarpal S.; Rezk, Sherif A.Aims. Epstein-Barr virus (EBV) expression has been reported in several hematopoietic and nonhematopoietic disorders but its expression in plasma cell neoplasms has been largely limited to immunodeficiency-related cases such as in the setting of post-organ transplantation or human immunodeficiency virus (HIV) infection. The aim of this study is to evaluate the association of EBV with plasma cell neoplasms, mainly in immunocompetent patients. Methods and results. We retrospectively studied 147 cases of patients with different plasma cell neoplasms (109 plasma cell myelomas, 22 plasmacytomas, and 16 monoclonal gammopathy cases). Six patients were immunocompromised. EBV was positive in 6 cases; 3 immunocompromised (2 patients with HIV infection and 1 patient was post-renal transplant) and 3 immunocompetent patients with plasmacytoma and variable plasmablastic features. Conclusions. Our data shows that EBV was negative in all plasma cell myeloma cases in immunocompetent patients and has an overall low association with the different plasma cell neoplasms in the immunocompetent setting. When expressed, it is usually associated with variable plasmablastic features.
- PublicationOpen AccessNext-generation sequencing-based characterization of the invasion by anatomical contiguity in a primary osseous diffuse large B-cell lymphoma. Correlation between the genetic profile of the malignancy and the clinical outcome of the patient(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Zaharie, Florin; Pop, Laura-Ancuta; Petrushev, Bobe; Jurj, Ancuta; Muresan, Mihai-Stefan; Eniu, Dan; Fetica, Bogdan; Petkov, Bozhidar; Pasca, Sergiu; Piciu, Doina; Rus, Ioana; Deak, Dalma; Dima, Delia; Desmirean, Minodora-Silvia; Tomuleasa, Ciprian; Berindan-Neagoe, IoanaPrimary bone lymphoma is now a welldescribed entity in the World Health Organization (WHO) Classification of Tumors of Soft Tissue and Bone as a malignancy of the lymphoid tissue, with at least one mass within bone, without involvement of supraregional lymph nodes or other extranodal sites. In the current paper, we describe the complete characterization of the mutational landscape of a diffuse large B cell non-Hodgkin's lymphoma (DLBLCL) of the tibial plateau. Currently, there is very little data about the genetic landscape of primary osseous lymphomas and about the genetic background of this type of malignancy, resistant to chemotherapy and invading the surrounding tissues. In the current paper, we describe the complete characterization of the mutational landscape of a DLBCL of the tibial plateau. Our data is consistent with already published data, that have shown that MKI67 activation is correlated with lymphoma progression. Along with a high Ki67 index, resistance to chemotherapy occurs with neurogenic locus notch homolog protein 1 (Notch) and KRAS activation. This is the first molecular characterization for the invasion by anatomical contiguity for a primary bone lymphoma and while we only characterized one case and further deep sequencing analyses are required, we can explain the clinical dismal evolution of the patient by correlating them with the genetic landscape of this type of lymphoma.
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