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Cytoplasmic Expression (cytoplasmic + expression)
Selected AbstractsSkp2 and p27kip1 expression in melanocytic nevi and melanoma: an inverse relationship,JOURNAL OF CUTANEOUS PATHOLOGY, Issue 10 2004Qing Li Background:, S-phase kinase associated protein-2 (Skp2) ubiquitin ligase p45SKP2 is important in the degradation of p27kip1 (a cyclin dependent kinase inhibitor) and progression through the G1-S cell-cycle checkpoint. Low levels of p27 and high levels of Skp2 are related to poor prognosis in some cancers. Methods:, Clinicopathologic features and immunohistochemical expression of Skp2 and p27kip1 were investigated in 198 melanocytic proliferations: 21 melanocytic nevi, 23 melanoma in situ, 119 primary melanoma, and 35 metastatic melanoma samples. Comparative and survival analyses were performed. Results:, Progressive and significant increases and decreases in the nuclear expression of Skp2 and p27kip1, respectively, was identified moving from melanocytic nevi (0.05 ± 0.2/85 ± 15) to melanoma in situ (3 ± 2/45 ± 20) to primary cutaneous melanoma (12 ± 9/30 ± 25) to metastatic melanoma (25 ± 15/15 ± 20) (p , 0.006). Expression of these proteins also significantly correlated with increasing American Joint Committee on Cancer (AJCC) T (tumor) classification and AJCC stage (p , 0.01). Moreover, the level of these two proteins exhibited a significant inverse relationship (r = ,0.4, p = 0.0001). Skp2 cytoplasmic labeling index of >20% predicted worse 10-year overall survival (38% vs. 86%, p = 0.04) in primary melanoma. Neither p27 nor Skp2 nuclear expression impacted significantly on prognosis. Conclusions:, Gain of Skp2 and loss of p27kip1 protein expression are implicated in melanoma progression where the level of p27kip1 may be regulated by targeted proteolysis via Skp2. Cytoplasmic expression of Skp2 defines a subset of aggressive melanomas and could represent another pathway of deregulation of the cell cycle. [source] Loss of CD20 expression in relapsed lymphomas after rituximab therapyEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2003Joud H. Haidar Abstract: The response rate at relapse to rituximab in prior responders B-cell non-Hodgkin's lymphoma (NHL) patients is below 50%. Loss of CD20 expression after rituximab therapy may explain this secondary resistance. However, the frequency of CD20 negative relapses cannot be assessed since most patients that relapsed after rituximab therapy have not been re-biopsied. Here, we present two patients with CD20 positive low grade B-cell NHL that lost the cell surface and cytoplasmic expression at relapse after rituximab therapy. Our findings suggest that confirmation of CD20 expression on the malignant B cells is required whenever rituximab therapy is considered. [source] Biological role of NHERF1 protein expression in breast cancerHISTOPATHOLOGY, Issue 5 2009Anita Mangia Aims:, To determine the role of Na+/H+ exchanger regulatory factor (NHERF1) in breast cancerogenesis and progression. Methods and results:, NHERF1 expression was examined in normal tissue, ductal carcinoma in situ (DCIS), invasive carcinoma (IBC), synchronous metastatic lymph node and metachronous distant metastases of a retrospective series of breast cancers. Fifty-one IBC, 42 DCIS and normal tissues were examined immunohistochemically, and the colocalization between NHERF1 and HER2/neu was studied by immunofluorescence. NHERF1 showed a different localization and pattern of expression in the different compartments of the breast. The mean value of cytoplasmic NHERF1 expression in paired samples was significantly higher in DCIS, IBC, distant metastases and metastatic lymph nodes with respect to normal tissues. Moreover, in metastatic lymph nodes NHERF1 was exclusively cytoplasmic. In the membrane NHERF1 was colocalized with overexpressed HER2/neu in DCIS, IBC and distant metastases. Conclusions:, Breast cancerogenesis is characterized by increased cytoplasmic expression of NHERF1 as the tumour progresses, suggesting a role in this process. The switch from apical membranous to cytoplasmic expression is compatible with a dual role for NHERF1 as a tumour suppressor or tumour promoter dependent on its subcellular localization. [source] Increased expression of SDF-1/CXCR4 is associated with lymph node metastasis of invasive micropapillary carcinoma of the breastHISTOPATHOLOGY, Issue 6 2009Fangfang Liu Aims:, Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 are implicated in tumour chemotaxis and metastasis. The aim was to examine their roles in the metastasis of invasive micropapillary carcinoma (IMPC) of the breast, a tumour with a high propensity for nodal spread. Methods and results:, We compared the expression of SDF-1 and CXCR4 in 103 cases of breast cancer containing IMPC components with a control group of 96 cases of invasive ductal carcinoma (IDC), not otherwise specified type by immunohistochemistry and chemical in situ hybridization (CISH). The results showed that the predominant cytoplasmic expression of both SDF-1 and CXCR4 was greater in tumour cells of the IMPC components than in those of the non-IMPC components and the control IDC cases, and was correlated significantly with the number of positive lymph nodes (P < 0.05). SDF-1 expression on cell membranes was less frequently identified in IMPC than IDC (P = 0.021). Immunohistochemical detection of SDF-1 in endothelial cells of lymphatic vessels was more common in IMPC (P = 0.007) and correlated significantly with lymph node status (P = 0.002), although SDF-1 mRNA was rarely detected by CISH. Conclusions:, This study suggests that up-regulation of cytoplasmic expression of SDF-1/CXCR4 might be one of the molecular mechanisms facilitating lymph node metastasis of IMPC. [source] The expression of Wilms' tumour-1 and Ca125 in invasive micropapillary carcinoma of the breastHISTOPATHOLOGY, Issue 6 2007A H S Lee Aim:, Metastases from ovarian serous papillary carcinoma to the breast and primary invasive micropapillary carcinoma of the breast are histologically similar. The distinction is clinically important to ensure appropriate management. Wilms' tumour-1 (WT1) and Ca125 are frequently expressed in serous papillary carcinomas, and uncommonly in unselected mammary carcinomas. One previous study found Ca125 expression in 69% of invasive micropapillary carcinomas. The aim was to assess the frequency of expression of WT1 and Ca125 in invasive micropapillary carcinoma. Methods and results:, Twenty-five of 34 invasive micropapillary carcinomas showed no nuclear expression of WT1. The remaining nine tumours showed weak to moderate immunoreactivity in 1,10% of nuclei. Six of these nine tumours also contained ductal carcinoma in situ, which expressed WT1 in five of the six. Membranous or cytoplasmic expression of Ca125 was found in seven tumours. Conclusion:, Nuclear WT1 expression is present in a minority of invasive micropapillary carcinomas and, when present, expression is focal. The frequency of expression of Ca125 was similar to the results in unselected mammary carcinoma. Thus, these markers are useful members of the immunohistochemical panel for the distinction of mammary invasive micropapillary carcinoma from ovarian serous papillary carcinoma. [source] The expression pattern of MUC1 (EMA) is related to tumour characteristics and clinical outcome in ,pure' ductal carcinoma in situ of the breastHISTOPATHOLOGY, Issue 2 2007M A J De Roos Aims:, To classify MUC1 according to five predefined expression patterns in ductal carcinoma in situ (DCIS) and related clinicopathological parameters, coexpression of other biological markers and prognosis. Methods and results:, With a manual tissue arrayer, 92% (n = 80) of the 87 DCIS samples were successfully targeted. Immunohistochemistry was carried out for MUC1, oestrogen receptor (ER), progesterone receptor (PR), Her2/Neu, p53 and cyclin D1. Entire membrane expression was related to Her2/neu negativity (P =0.042). Apical membrane expression was associated with low grade (P = 0.027), Her2/neu negativity (P = 0.014) and PR positivity (P = 0.005). Focal cytoplasmic expression was related to high grade (P = 0.006). Diffuse cytoplasmic expression was associated with high grade (P = 0.004), large tumour size (P = 0.046), Her2/neu positivity (P =0.042) and cyclin D1 positivity (P = 0.002). On the basis of these analyses the four patterns were reclassified as membranous or cytoplasmic expression. On multivariate analysis, cytoplasmic MUC1 expression (hazard ratio 8.5, 95% confidence interval 1.0, 73.0; P = 0.04) was the only independent predictor of local recurrence. Conclusions:, Four patterns of MUC1 expression are recognized in DCIS that suggest a relationship to functional differentiation and can be simplified into two types that are clinically relevant and could therefore be helpful in the distinction between different subgroups of DCIS. [source] Nuclear survivin is associated with disease recurrence and poor survival in patients with cutaneous malignant melanomaHISTOPATHOLOGY, Issue 7 2007F Piras Aims:, Survivin is expressed in neoplastic cells and appears to be associated with resistance to therapy and shorter survival in various types of tumours. The aim of the present study was to determine whether nuclear or cytoplasmic expression of survivin is related to disease recurrence and overall survival of patients with Stage I and II melanoma according to the American Joint Committee on Cancer (AJCC) staging system. Methods and results:, Immunohistochemistry was performed on formalin-fixed paraffin-embedded sections of primary cutaneous melanoma from 50 patients. Survival rates were estimated using the Kaplan,Meier method and compared using the log rank test. Association of clinical variables (gender, age, tumour location, thickness, Clark level and AJCC stage) with survivin expression was analysed by Fisher's exact test. Patients with nuclear immunoreactivity for survivin had an increased risk of disease recurrence during the first three postoperative years (P < 0.05) and of death (P < 0.05). Cytoplasmic immunoreactivity was not correlated with either survival or clinical variables. Conclusions:, Nuclear presence of survivin may be an independent biomarker for disease recurrence and overall survival in patients with Stage I and II melanoma. [source] Expression of HuR in Merkel cell carcinoma and in normal skinJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2008Virve Koljonen Background:, HuR is a ubiquitously expressed member of the Elav/Hu family of mRNA-binding proteins, and its cytoplasmic expression has been recognised to participate in carcinogenesis. The aims of this study were to explore the expression pattern of HuR in primary Merkel cell carcinoma (MCC), lymph node metastases and non-neoplastic skin. Methods:, Twenty-two primary MCC samples and five lymph node metastases were evaluated for HuR expression by immunohistochemistry. The data were compared with clinical parameters. Results:, Nuclear and cytoplasmic HuR-staining patterns were observed. Nuclear immunoreactivity was observed in 91% of the primary tumors and in 80% of the lymph node metastases. Cytoplasm was positive in 27% of the primary tumors and in 60% of the lymph node metastases. No cytoplasmic HuR immunoreactivity was detected in non-neoplastic skin. However, moderate to strong nuclear staining was found in normal epidermis and in the epithelium of hair follicles and sebaceous glands. Expression of HuR in MCC did not associate with clinicopathological parameters. Conclusions:, Primary MCCs and their lymph node metastases as well as non-neoplastic skin show nuclear expression of HuR protein. In contrast to non-neoplastic skin, a subset of MCC tumors show cytoplasmic HuR staining, which may contribute to carcinogenesis in MCC. [source] Involvement of nuclear factor-kappa B in bcl-xL-induced interleukin 8 expression in glioblastomaJOURNAL OF NEUROCHEMISTRY, Issue 3 2008Chiara Gabellini Abstract We recently reported that bcl-xL regulates interleukin 8 (CXCL8) protein expression and promoter activity in glioblastoma cells. In this paper we demonstrate that CXCL8 induction by bcl-xL is mediated through a nuclear factor-kappa B (NF-kB)-dependent mechanism. Mutational studies on the CXCL8 promoter showed that NF-kB binding site was required for bcl-xL-induced promoter activity and an enhanced nuclear expression of NF-kB subunits p65 and p50 was observed after bcl-xL over-expression. Electrophoretic mobility shift assay showed an increased DNA-binding activity of NF-kB in bcl-xL over-expressing cells and the use of specific antibodies confirmed the involvement of p65 and p50 in NF-kB activity on CXCL8 promoter sequence. NF-kB activity regulation by bcl-xL involved IkB, and IKK complex signaling pathway. In fact, bcl-xL over-expression induced a decrease of cytoplasmic expression of the IkB, protein, paralleled by an increase in the phosphorylation of the same IkB, and IKK,/,. Moreover, the down-regulation of the ectopic or endogenous bcl-xL expression through RNA interference confirmed the ability of bcl-xL to modulate NF-kB pathway, and the transient expression of a degradation-resistant form of the cytoplasmic NF-kB inhibitor IkB, in bcl-xL transfectants confirmed the involvement of that inhibitor in bcl-xL-induced CXCL8 expression and promoter activity. In conclusion, our results demonstrate the role of NF-kB as the mediator of bcl-xL-induced CXCL8 up-regulation in glioblastoma cells. [source] Calgizarrin like gene (Cal) deficient mice undergo normal spermatogenesisMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 4 2003Ashraf U. Mannan Abstract The murine calgizzarin like gene (Cal) encodes for a calcium binding protein, which belongs to the S100 family of EF-hand proteins. It is specifically expressed in Sertoli cells in the testis and its expression is down-regulated by unknown factor(s) from spermatocytes/spermatids. In this paper, we show by transfection of a fusion protein of green fluorescent protein and Cal protein into NIH3T3 cells, that the expression of Cal is restricted only in the cytoplasm of the cell. A differentially regulated cytoplasmic expression of the Cal in Sertoli cells during mouse development suggests that Cal might play an important role during spermatogenesis. In order to elucidate the function of the Cal protein in the spermatogenesis, we disrupted the Cal locus in mouse by homologous recombination. In our knockout mouse, we deleted exon 2 and exon 3 of the Cal gene and replaced them with a neomycin cassette, which resulted in a complete loss of the Cal transcript. Male and female Cal4+/, and Cal4,/, mice from genetic backgrounds C57BL/6J,× 129X1/SvJ hybrid and 129X1/SvJ inbred exhibited normal phenotype and were fertile. An intensive phenotypic analysis showed no gross abnormalities in testis morphology. The lack of the Cal protein also does not affect the parameters of sperm, as they are able to fertilize the oocytes in a competent manner, which is comparable to wild-type sperm. Collectively our results demonstrate that Cal is a nonessential protein and it does not play an important role in mouse spermatogenesis or in process of fertilization. Mol. Reprod. Dev. 66: 431,438, 2003. © 2003 Wiley-Liss, Inc. [source] LRRK2 is a component of granular alpha-synuclein pathology in the brainstem of Parkinson's diseaseNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 3 2008J. Alegre-Abarrategui Classical Parkinson's disease (PD) is characterized by the appearance of Lewy bodies (LBs) in affected brain regions, showing mostly compact alpha-synuclein deposition, in contrast with punctate or granular deposition, hypothesized to represent early stages of aggregation. Leucine-rich repeat kinase 2 (LRRK2) is the commonest mutated gene in inherited and idiopathic PD. LRRK2 mutation carriers display a diverse neuropathology, including alpha-synuclein and tau inclusions, suggesting an upstream role for LRRK2 in protein aggregation. We studied LRRK2 expression throughout the normal human brain with three different antibodies. We also examined the pattern of LRRK2 expression in relation to alpha-synuclein aggregation and LB formation in the brainstem of sporadic LB disease. Physiological LRRK2 expression was not restricted to regions preferentially affected in PD and LRRK2 often localized to the nuclear envelope in addition to the known cytoplasmic expression. In PD, we were able to consistently detect LRRK2 in the halo of a minority (approximately 10%) of nigral LBs using three different antibodies. Only one antibody detected LRRK2 in the core of approximately 80% of classic LBs. In the lower brainstem, most notably in the dorsal motor nucleus of the vagus, we found previously unrecognized LRRK2 labelling of complex globular lesions, filled with LB-like matter showing a punctate or granular staining for alpha-synuclein. This was often accompanied by strong LRRK2 expression within dystrophic neurites. Our findings confirm widespread physiological LRRK2 expression in the human brain and suggest an association of LRRK2 with possible early-stage alpha-synuclein pathology in the brainstem of PD. [source] Increased cytoplasmic S100A6 expression is associated with pulmonary adenocarcinoma progressionPATHOLOGY INTERNATIONAL, Issue 9 2009Aya Ishii S100A6 is a calcium-binding protein implicated in many cellular processes and frequently upregulated in cancer. Recently it was reported that S100A6 is one of the genes having higher expression in adenocarcinoma mixed subtype with a bronchioloalveolar carcinoma (BAC) component than in pure BAC. To clarify the association of S100A6 expression with stepwise progression of lung adenocarcinoma, S100A6 protein expression was examined on immunohistochemistry in 92 formalin-fixed and paraffin-embedded lung adenocarcinomas. Both the nucleus and cytoplasm of the tumor cells were stained, and the nuclear and cytoplasmic expression of S100A6 was assessed individually. In addition, six frozen surgical specimens were selected, and the expression of S100A6 was confirmed on western blotting. As a result, although it was not possible to detect any significant correlation between nuclear S100A6 immunoreactivity and tumor progression, advanced adenocarcinoma had significantly higher cytoplasmic S100A6 expression than non-invasive lesions or normal lung tissue (P < 0.05). Moreover, the BAC component tended to have weaker staining than any of the other components. These findings indicate that S100A6 may be associated with the stepwise progression and/or invasion of lung adenocarcinoma, especially BAC-type adenocarcinoma. The present results suggest the utility of S100A6 immunohistochemistry as a marker for estimation of malignancy in adenocarcinoma with a BAC component. [source] Altered expression of MUTYH and an increase in 8-hydroxydeoxyguanosine are early events in ulcerative colitis-associated carcinogenesis,THE JOURNAL OF PATHOLOGY, Issue 1 2009Masaki Gushima Abstract 8-Hydroxy-guanine (8-OH-G) mismatches readily with adenine residues, leading to a G : C to T : A transversion mutation. The human mutY homologue (MUTYH) excises adenine misincorporated opposite 8-OH-G during replication and suppresses mutations caused by reactive oxygen species. We defined the expression of 8-hydroxydeoxyguanosine (8-OHdG) and MUTYH in ulcerative colitis (UC)-associated neoplasia by immunohistochemistry and compared this with expression in UC patients without neoplasia and patients unaffected by UC. We also performed mutation analyses for MUTYH and K- ras. 8-OHdG was expressed more intensely in the mucosa of UC-associated neoplasia and UC without neoplasm than in the mucosa unaffected by UC. Immunohistochemistry with two different types of MUTYH antibody showed that UC-associated neoplasia and UC without neoplasia exhibited strong cytoplasmic expression and attenuated nuclear expression of MUTYH when compared with patients unaffected by UC. No pathological MUTYH mutations were detected in any of the UC-associated neoplasia cases. However, K- ras mutation was detected in two cases, one of which showed G : C to T : A transversion mutation and attenuated nuclear staining of MUTYH. In conclusion, inflamed mucosa of UC is exposed to oxidative damage. An increase in cytoplasmic MUTYH, rather than its mutation, may contribute to the promotion of carcinogenesis in UC. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Epithelial to Mesenchymal Transition During Late Deterioration of Human Kidney Transplants: The Role of Tubular Cells in FibrogenesisAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2005Attapong Vongwiwatana The hallmark of failing renal transplants is tubular atrophy and interstitial fibrosis (TA/IF). Injury to tubular epithelial cells (TEC) could contribute to fibrogenesis via epithelial,mesenchymal transition (EMT). We examined the features of EMT in renal transplants that developed TA/IF. Biopsies from 10 allograft kidneys with impaired function and TA/IF and 10 biopsies from transplants with stable function were compared to their implantation biopsies. Relative to implantation biopsies, TEC in TA/IF kidneys showed loss of epithelial markers (E-cadherin, cytokeratin) with altered distribution. Some TEC also showed new cytoplasmic expression of mesenchymal markers vimentin, S100A4, and alpha smooth muscle actin (,-SMA) and collagen synthesis marker heat shock protein (HSP-47), both in deteriorating and atrophic tubules. Double immunostaining showed coexpression of cytokeratin and vimentin, S100A4 and HSP-47, indicating intermediate stages of EMT in TA/IF. These changes were absent or much less in transplants with stable function. EMT features in the TA/IF group correlated with serum creatinine (vimentin, S100A4, HSP-47), history of T-cell-mediated rejection (cytokeratin, S100A4) and proteinuria (cytokeratin). These findings support a model in which the TEC damage induces loss of epithelial features and expression of fibroblast features, as a common pathway of deterioration by either immunologic or nonimmunologic processes. [source] | |||||||||||||