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Clinicopathological Parameters (clinicopathological + parameter)
Selected AbstractsChromatin assembly factor-1 (CAF-1)-mediated regulation of cell proliferation and DNA repair: a link with the biological behaviour of squamous cell carcinoma of the tongue?HISTOPATHOLOGY, Issue 7 2007S Staibano Aims:, Squamous cell carcinoma (SCC) of the tongue shows aggressive behaviour and a poor prognosis. Clinicopathological parameters fail to provide reliable prognostic information, so the search continues for new molecular markers for this tumour. Chromatin assembly factor-1 (CAF-1) plays a major role in chromatin assembly during cell replication and DNA repair and has been proposed as a new proliferation marker. The aim of this study was to investigate its expression in SCC of the tongue. Methods and results:, The immunohistochemical expression of the p60 and p150 subunits of CAF-1 were evaluated in a series of SCCs of the tongue. The findings were correlated with the expression of proliferation cell nuclear antigen (PCNA) and patients' clinicopathological and follow-up data. CAF-1/p60 was expressed in all the tumours, whereas CAF-1/p150 was down-regulated in a number of cases. Overexpression of CAF-1/p60 and down-regulation of CAF-1/p150 identified SCCs with poor outcome, in addition to the classical prognostic parameters. Conclusions:, Simultaneous CAF-1-mediated deregulation of cell proliferation and DNA repair takes place in aggressive SCC of the tongue. Therefore, the evaluation of CAF-1 expression may be a valuable tool for evaluation of the biological behaviour of these tumours. This may be relevant to the introduction of improved follow-up protocols and/or alternative therapeutic regimens. [source] Differential expression of hMLH1 in sporadic human colorectal cancer tumors and distant metastasesAPMIS, Issue 11 2009NICOLAI BALLE LARSEN Somatic defects in the mismatch repair system constitute an important pathway in colorectal carcinogenesis. We have examined the expression of mismatch repair proteins in sporadic stage IV colorectal tumors and their derived metastases. Sporadic tumors were further examined for differences in expression between the tumor transition zone and the invasive front. Expression of hMSH2, hMLH1, and hPMS2 was screened immunohistochemically in 92 stage IV tumors and derived liver metastases. In cases with loss of mismatch repair protein expression, lymph node metastases were also examined. Clinicopathological parameters and Ki-67 staining indexes were evaluated and compared. Four tumors displayed a complete loss of hMLH1/hPMS2 expression at the transition zone; however, three of these expressed both proteins at the invasive front and in liver and lymph node metastases. A further four were predominantly hMLH1/hPMS2 negative at the transition zone, but with distinct subclones of hMLH1/hPMS2-expressing cells at the transition zone. All of these tumors expressed hMLH1/hPMS2 at the invasive front and in liver metastases, with three also expressing hMLH/hPMS2 in lymph node metastases. No significant difference in the proliferative index was observed for the hMLH1/hPMS2-compromised group. In stage IV tumors re-expression of hMLH1/hPMS2 occurred, leading to different patterns of expression within the primary tumor and between tumor and metastases. This may have functional importance for the chemosensitivity of metastases compared to the primary tumor. [source] Polymorphisms of tumour necrosis factors A and B in breast cancerINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2002K. S. Park Summary We assayed for germline single nucleotide polymorphisms (SNPs) in the TNFB and TNFA genes in patients with breast cancer. SNPs were observed in the first intron of TNFB (G/A) and at ,1031 (T/C), ,863 (C/A), ,857 (C/T) and ,308 (G/A) in the promoter region of TNFA from peripheral leucocytes in 95 breast cancer patients and 190 healthy subjects as controls. The TNFB*G/TNFB*G homozygote (23.2% vs. 5.8%, P= 0.001) was predominant in patients, while the TNFB*A/TNFB*A homozygote was less frequent in patients (34.7% vs. 46.3%, P = 0.041) than in the control subjects. Breast cancer was not associated with SNPs in the TNFA promoters. Although the TNFB SNP failed to associate with any clinicopathological parameter of breast cancer, a substantial difference in pathology among tumour stages for the ,857 SNP in TNFA was detected. These results indicate that TNFB has both tumorigenic and antitumorigenic capabilities depending on the genotype: the TNFB SNP TNFB*G/TNFB*G genotype gave an increased risk for breast cancer and that of TNFB*A/TNFB*A gave resistance to breast cancer (OR = 5.3395%; CI: 2.33,12.19). The results suggest that the TNFB*G allele plays some role in the tumorigenesis or activation of dormant tumour cells, but the TNFB*A allele induces some function(s) leading to the inhibition of tumorigenesis. [source] Peroxisome proliferator-activated receptor gamma in human prostate carcinomaPATHOLOGY INTERNATIONAL, Issue 5 2009Yasuhiro Nakamura Peroxisome proliferator-activated receptor (PPAR) is a member of the nuclear hormone receptor superfamily of transcription factors. Peroxisome proliferator-activated receptor gamma (PPAR,) plays an important role in the regulation of lipid homeostasis, adipogenesis, insulin resistance, and development of various organs. Agonists of PPAR, have been also reported to inhibit proliferation of prostate carcinoma cells as in other human malignancies, and these synthetic ligands have been used in differentiation-mediated therapy of various human carcinomas associated with high levels of PPAR,. The significance of PPAR, expression, however, was unknown in human prostate carcinoma tissues. The purpose of the present study was therefore to examine the immunolocalization of PPAR, in human prostate cancer tissues (40 cases) and correlate the findings with clinicopathological features of the patients in order to evaluate its possible biological significance. Twenty-nine patients were positive for PPAR, immunoreactivity (73%) and a significant inverse correlation was detected between PPAR, immunoreactivity, pT stage (P = 0.036), and serum concentration of prostate-specific antigen (P = 0.0004). In conclusion, PPAR, immunoreactivity is considered to be a new clinicopathological parameter of human prostate cancer. [source] Molecular characterization of tumour heterogeneity and malignant mesothelioma cell differentiation by gene profilingTHE JOURNAL OF PATHOLOGY, Issue 1 2005Xiaojuan Sun Abstract Malignant mesothelioma is an aggressive tumour, characterized by a variable differentiation pattern and poor prognosis. At present, the clinical outcome in patients with malignant mesothelioma is mainly predicted by the morphological phenotype of the tumour. However, this conventional clinicopathological parameter is of limited value, partly because of the biological heterogeneity of this tumour and poor understanding of the regulatory mechanisms underlying the various patterns of growth. To elucidate the intrinsic molecular programmes that determine tumour differentiation, oligonucleotide arrays were used in an in vitro model of mesothelioma differentiation. The analysis of 2059 genes detected 102 genes that were significantly deregulated. Clustering of these genes into functional categories showed distinctive patterns for the two phenotypes, namely epithelioid and sarcomatoid. The molecular fingerprint of the sarcomatoid tumour component indicates overrepresentation of growth factor receptors and growth factor binding proteins, whereas epithelioid mesothelioma cells express other tumour-promoting factors involved in differentiation, metabolism, and regulation of apoptosis. These differences in the molecular phenotype may give a better basis for diagnosis and for designing novel therapies. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Expression of EMMPRIN and matriptase in esophageal squamous cell carcinoma: Correlation with clinicopathological parametersDISEASES OF THE ESOPHAGUS, Issue 6 2006M.-F. Cheng SUMMARY., Extracellular matrix metalloproteinase inducer (EMMPRIN) and the type II transmembrane serine protease, matriptase, are expressed in several human cancers and play an important role in tumor progression. The aim of the present study was to investigate the immuno-staining patterns of EMMPRIN and matriptase in patients with esophageal squamous cell carcinomas (SCC) and correlate the percentage tumor staining with tumor differentiation and clinical parameters. EMMPRIN and matriptase immunoreactivity was seen on the cell membrane and in the cytoplasm of tumor cells in all 41 cases of esophageal SCC evaluated. The percentage tumor staining of EMMPRIN was 48 ± 3% for well differentiated, 73 ± 3% for moderately differentiated, and 92 ± 3% for poorly differentiated esophageal SCC. Higher percentage tumor staining with EMMPRIN correlated significantly with poorly differentiated esophageal SCC (P < 0.05). The percentage tumor staining with matriptase correlated significantly with tumor differentiation (52 ± 3% for well differentiated, 85 ± 2% for moderately differentiated, and 88 ± 3% for poorly differentiated esophageal SCC). Additionally, higher percentage tumor staining with matriptase was significantly correlated with the advanced N and M stages (P < 0.05). Our results demonstrate that EMMPRIN and matriptase are over-expressed in esophageal SCC and are correlated with advanced clinicopathological stages. Pharmacological agents targeting EMMPRIN and matriptase expressions may be beneficial in the treatment of esophageal SCC. [source] Expression of c-MET, low-molecular-weight cytokeratin, matrix metalloproteinases-1 and -2 in spinal chordomaHISTOPATHOLOGY, Issue 5 2009Takahiko Naka Aims:, In skull base chordoma, c-MET expression has been reported to correlate with younger patient age and favourable prognosis; however, it also contributes to tumour invasiveness, especially in recurrent lesions, suggesting variable roles for c-MET according to clinical status. The aim of this study was to investigate the significance of c-MET expression in spinal chordoma, which affects patients who are 10,20 years older than those with skull base chordoma. Methods and results:, Using immunohistochemical techniques, the expression of c-MET and its ligand, hepatocyte growth factor (HGF) was investigated in 34 primary spinal chordomas and compared with other clinicopathological parameters. Expression of c-MET and HGF was observed in 85.3 and 21.7% of lesions, respectively. c-MET expression correlated with the expression of an epithelial marker, low-molecular-weight cytokeratin (CAM5.2). Lesions with higher c-MET expression showed significantly stronger expression of proteinases, including matrix metalloproteinase (MMP)-1 and MMP-2. However, c-MET expression was not associated with patient age, proliferative ability estimated by MIB-1 labelling index, or prognosis. Conclusions:, c-MET expression was observed in most spinal chordomas and correlated with the expression of CAM5.2, suggesting a relationship to an epithelial phenotype. [source] Activated Stat3 expression in gestational trophoblastic disease: correlation with clinicopathological parameters and apoptotic indicesHISTOPATHOLOGY, Issue 2 2008H Y Chan Aims:, To assess the expression profile of the activated form of signal transducer and activator of transcription (Stat)3 in gestational trophoblastic disease (GTD) and correlate the findings with clinicopathological parameters. Methods and results:, By immunohistochemistry, both cytoplasmic and nuclear expression of p-Stat3-Ser727 was demonstrated in 88 trophoblastic tissues, including placentas and GTD. Nuclear immunoreactivity of p-Stat3-Ser727 was significantly higher in hydatidiform mole (HM) (P < 0.001) and choriocarcinoma (P = 0.009) when compared with normal placentas. Placental site trophoblastic tumours (PSTT) and epithelioid trophoblastic tumours (ETT) also demonstrated higher nuclear p-Stat3-Ser727 expression than their normal trophoblast counterparts. Higher p-Stat3-Ser727 expression was confirmed in choriocarcinoma cell lines, JEG-3 and JAR, than in a normal trophoblast cell line, with both nuclear and cytoplasmic fractions demonstrated by immunoblotting. Spontaneously regressed HM showed significantly increased nuclear and cytoplasmic p-Stat3-Ser727 immunoreactivity over those that developed gestational trophoblastic neoplasia (GTN) (P = 0.013, P = 0.039). There was a significant positive and inverse correlation between nuclear p-Stat3-Ser727 immunoreactivity and apoptotic indices [terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labelling and M30 CytoDeath antibody] (P = 0.001, P < 0.001, Spearman's , test) and Bcl-2 expression (P = 0.034), respectively. Conclusions:, p-Stat3-Ser727 plays a role in the pathogenesis of GTD, probably through the regulation of apoptosis. p-Stat3-Ser727 immunoreactivity is a potential marker in predicting GTN in HM. [source] Down-regulation of ATBF1 is a major inactivating mechanism in hepatocellular carcinomaHISTOPATHOLOGY, Issue 5 2008C J Kim Aims:, ,-Fetoprotein (AFP) is frequently detected in hepatocellular carcinomas (HCCs) and AT motif binding factor 1 (ATBF1) down-regulates AFP gene expression in hepatic cells. The ATBF1 gene also inhibits cell growth and differentiation, and altered gene expression is associated with malignant transformation. The aim was to investigate the potential role of the ATBF1 gene in HCCs. Methods and results:, Somatic mutations, allelic loss and hypermethylation of the ATBF1 gene were analysed in 76 sporadic HCCs. The level of ATBF-1 mRNA expression was analysed using quantitative real-time reverse transcriptase-polymerase chain reaction. Genetic studies of the ATBF1 gene revealed absence of somatic mutation in the hotspot region and 15 (25%) of 60 informative cases showed allelic loss at the ATBF1 locus. Hypermethylation in the intron 1 region of the ATBF1 gene was detected in only one case. Interestingly, ATBF1 mRNA expression in HCCs was significantly reduced in 55 (72.4%) samples compared with the corresponding surrounding liver tissues. Reduced expression was not statistically associated with clinicopathological parameters including stage, histological grade, infective virus type, and serum ,-fetoprotein level. Conclusions:, The ATBF1 gene may contribute to the development of HCCs via transcriptional down-regulation of mRNA expression, but not by genetic or epigenetic alterations. [source] c-FLIP expression in colorectal carcinomas: association with Fas/FasL expression and prognostic implicationsHISTOPATHOLOGY, Issue 2 2007P Korkolopoulou Aims:, Disruption of apoptotic cell death has been implicated in tumour aggressiveness in colonic carcinogenesis. The Fas,Fas ligand (FasL) system is involved in the execution of apoptosis induced by the immune system. c-FLIP protein constitutes an inhibitor of Fas and other (TRAIL) death receptor-mediated apoptosis. The aim of this study was to investigate the simultaneous expression of Fas, FasL and c-FLIP in relation to standard clinicopathological parameters and patients' outcome in colorectal cancer. Methods and results:, Levels of Fas, FasL and c-FLIP protein expression were quantified immunohistochemically in paraffin-embedded tissues from 90 patients. Immunopositivity was detected for Fas, FasL and c-FLIP in 71%, 35.5% and 68.8% of cases, respectively. Concurrent expression of Fas/FasL was seen in 28 samples (31%), of which 24 (85.7%) also displayed c-FLIP positivity (P = 0.04). c-FLIP overexpression (> 10%) tended to prevail marginally in higher stage tumours (P = 0.09). Additionally, FasL and c-FLIP adversely affected survival on both univariate (P = 0.001 and P = 0.0024, respectively) and multivariate analysis [hazard ratio (HR) 3.491, P = 0.005 and HR 2.960, P = 0.036, respectively]. Conclusions:, The frequent expression and coexpression of Fas, FasL and c-FLIP in colorectal carcinoma implicates c-FLIP as an inhibitor of the Fas,FasL-induced death pathway in these tumours. Moreover, c-FLIP conveys independent prognostic information in the presence of classical prognosticators. [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] Prognostic indicators of gastric carcinoma confined to the muscularis propriaHISTOPATHOLOGY, Issue 1 2007H Son Aims:, Gastric carcinoma confined to the muscularis propria (MPGC) is considered an intermediate-stage carcinoma. A method of discriminating between more favourable and less favourable prognostic groups of this entity is critically needed in dealing with this heterogeneous disease. The aim of this study was to examine the correlation between survival of patients with MPGC and its various clinicopathological parameters. Methods and results:, Various clinicopathological parameters were studied in 171 tissue samples including: macroscopic appearance, size, age, sex, stage, invasion depth, Lauren and Ming classifications, extent, lymphatic emboli and nodal metastasis. Tumours macroscopically resembling early gastric cancers, younger patient age, absence of lymphatic tumour emboli and lower stage were significantly associated with better prognosis of MPGC by univariate analysis. Tumours macroscopically resembling early gastric cancers, younger patient age and Lauren's diffuse type were significantly associated with a better prognosis of MPGC by multivariate analysis. Conclusions:, These indicators are practical parameters for predicting patient prognosis in clinical practice. The description of these parameters should be carefully noted in the final report and pathologists should evaluate the macroscopic appearance of MPGC. [source] Type-specific roles of histone deacetylase (HDAC) overexpression in ovarian carcinoma: HDAC1 enhances cell proliferation and HDAC3 stimulates cell migration with downregulation of E-cadherinINTERNATIONAL JOURNAL OF CANCER, Issue 6 2010Akiko Hayashi Abstract Histone acetylation/deacetylation controls chromatin activity and subsequent gene transcription. Recent studies demonstrated the activation of histone deacetylases (HDACs) in various human malignancies; however, the expression and function of HDACs in ovarian tumors are not fully understood. In this study, we examined the immunohistochemical expression of HDAC1, HDAC2 and HDAC3 using tissues obtained from 115 cases of ovarian tumors and compared it with that of Ki-67 (a growth marker), p21, and E-cadherin and clinicopathological parameters. In addition, we analyzed the effect of specific siRNA for HDAC1, HDAC2 and HDAC3 on the expression of cell cycle-related molecules and E-cadherin to clarify the functional difference among the 3 HDACs. The results indicated that the immunohistochemical expression of nuclear HDAC1, HDAC2 and HDAC3 proteins increased stepwise in benign, borderline and malignant tumors. The expression of HDAC1 and HDAC2 was correlated with Ki-67 expression and that of HDAC3 was inversely correlated with E-cadherin expression. Among the HDACs examined, only HDAC1 was associated with a poor outcome, when overexpressed. Treatment with HDAC inhibitors suppressed the proliferation of ovarian cancer cells in association with apoptosis. A specific siRNA for HDAC1 significantly reduced the proliferation of ovarian carcinoma cells via downregulation of cyclin A expression, but siRNA for HDAC3 reduced the cell migration with elevated E-cadherin expression. Our results suggested that HDAC1 plays an important role in the proliferation of ovarian cancer cells, whereas HDAC3 functions in cell adhesion and migration. Therefore, specific therapeutic approaches should be considered according to the HDAC subtypes. [source] Expression of microRNA-221 is progressively reduced in aggressive prostate cancer and metastasis and predicts clinical recurrenceINTERNATIONAL JOURNAL OF CANCER, Issue 2 2010Martin Spahn Abstract Emerging evidence shows that microRNAs (miR) are involved in the pathogenesis of a variety of cancers, including prostate carcinoma (PCa). Little information is available regarding miR expression levels in lymph node metastasis of prostate cancer or the potential of miRs as prognostic markers in this disease. Therefore, we analyzed the global expression of miRs in benign, hyperplastic prostate tissue (BPH), primary PCa of a high risk group of PCa patients, and corresponding metastatic tissues by microarray analysis. Consistent with the proposal that some miRs are oncomirs, we found aberrant expression of several miRs, including the downregulation of miR-221, in PCa metastasis. Downregulation of miR-221 was negatively correlated with the expression of the proto-oncogen c-kit in primary carcinoma. In a large study cohort, the prostate-specific oncomir miR-221 was progressively downregulated in aggressive forms of PCa. Downregulation of miR-221 was associated with clinicopathological parameters, including the Gleason score and the clinical recurrence during follow up. Kaplan,Meier estimates and Cox proportional hazard models showed that miR-221 downregulation was linked to tumor progression and recurrence in a high risk prostate cancer cohort. Our results showed that progressive miR-221 downregulation hallmarks metastasis and presents a novel prognostic marker in high risk PCa. This suggests that miR-221 has potential as a diagnostic marker and therapeutic target in PCa. [source] Original Article: Clinical Investigation: Neuroendocrine differentiation in stage D2 prostate cancersINTERNATIONAL JOURNAL OF UROLOGY, Issue 5 2008Naoto Kamiya Objectives: Chromogranin A (CgA) and neuro-specific enolase (NSE) are gaining acceptance as markers of several types of neuroendocrine tumors and the concentration of CgA and NSE have been reported to be elevated in relation to neuroendocrine differentiation of prostate cancer. The aim of the present study was to examine the correlation between the immunohistochemical (IHC) findings and serum value for CgA and NSE in untreated stage D2 prostate cancer patients. Methods: Immunohistochemistry was carried out using antibodies against CgA and NSE in 58 patients and, pretreatment serum CgA and NSE levels were measured by monoclonal immunoradiometric assay in 18 patients with stage D2 prostate cancer treated by androgen ablation. We examined the relationship of the pretreatment serum level to IHC findings for CgA and NSE in prostate cancer patients to clinicopathological parameters, and prognosis. Also, we evaluated the correlation of IHC findings to serum levels for CgA and NSE. Results: There was a statistically significant correlation between CgA positivity and serum CgA level (P = 0.0421). However, there was no statistically significant correlation between NSE positivity and serum NSE level (P > 0.05). We divided stage D2 patients into three groups according to IHC positivity of CgA and NSE. The cause-specific survival was significantly poorer in patients with strongly positive (++) patients for independent CgA and combined CgA with NSE (P = 0.0379). Multivariate analysis of cause-specific survivals in patients with stage D2 prostate cancer demonstrated that strong IHC stain was considered as independent variable associated with greater risk of death (P = 0.0142). Conclusion: Neuroendocrine differentiation in stage D2 prostate cancer has attracted considerable attention as a potentially findings prognosis. Thus, CgA had a stronger relationship between serum levels and IHC positivity in contrast to NSE, suggesting clinical usefulness as a tumor marker in predicting the extent of neuroendocrine differentiation in prostate cancer. [source] Elevated serum level and gene polymorphisms of TGF-,1 in gastric cancerJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 3 2008Xue Li Abstract Transforming growth factor (TGF)-,1, as a candidate tumor marker, is currently of interest. In this study, serum TGF-,1 levels in gastric cancer (GC) patients and healthy volunteers were measured using enzyme-linked immunosorbent assay (ELISA). In addition, single nucleotide polymorphisms (SNPs) of the TGF-,1 gene at codon 10 and codon 25 were identified by means of amplification refractory mutation system,polymerase chain reaction (ARMS-PCR) and sequence analysis. Our results indicated that serum concentrations of TGF-,1 in GC patients were significantly higher than those in the control, and positively correlated with tumor mass, invasion, metastasis, and clinical stage. The serum TGF-,1 levels of patients recovering from radical resection were markedly lower than those before surgery. Meanwhile, no deoxyribonucleic acid (DNA) sequence variation at codon 25 of the TGF-,1 gene was found and a TGF-,1 gene polymorphism at codon 10 did not show obvious correlations with either TGF-,1 expression or clinicopathological parameters of GC. Our evidence suggested that serum concentration of TGF-,1 might be a novel tumor marker for GC and the polymorphisms of TGF-,1 gene did not play a role as a determinant of serum TGF-,1 concentration or as a genetic risk factor in the gastric carcinogenesis and progression. J. Clin. Lab. Anal. 22:164,171, 2008. © 2008 Wiley-Liss, Inc. [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] Matrix metalloproteinase-1 promoter polymorphism and epithelial ovarian cancer: Does ethnicity matter?JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 2 2007Woong Ju Abstract Aim:, To estimate the relationship between matrix metalloproteinase (MMP)-1 promoter -1607 bp polymorphism and the risk of epithelial ovarian cancer (EOC) in Korean women and to clarify the ethnic difference in genotype distribution of this polymorphism. Methods:, Single nucleotide polymorphism (SNP) of MMP-1 promoter -1607 region in 133 EOC patients and 332 cancer-free patients were investigated. Then the associations of this polymorphism with EOC or its clinicopathological parameters were analyzed. In addition, genotype distributions of this polymorphism in Korean women were compared with those of other races by extracting data from the previously published literature. Results:, We found no relationship between MMP-1 promoter -1607 bp polymorphism and epithelial ovarian cancer in a Korean population. Furthermore, we found ethnicity-dependent differences in genotype distributions and allele frequencies by comparison with previous articles on this topic. We report significant ethnic differences in the genotype distributions and allele frequencies of the MMP-1 promoter -1607 bp polymorphism. Conclusion:, Our results indicate that MMP-1-1607 bp polymorphism shows ethnic diversity, and that the hypothesis that this polymorphism is associated with epithelial ovarian cancer is not supported by this study in a Korean population. Moreover, this finding concurs with results obtained in white Americans and Europeans. [source] The expression of NMDA receptor 1 is associated with clinicopathological parameters and prognosis in the oral squamous cell carcinomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 9 2004S.-W. Choi Background:, Glutamate activates the N -methyl- d -aspartate (NMDA) receptors and this receptor is involved in the proliferation and migration of various tumour cells in vitro. However, the relationship between NMDA receptor expression and clinical parameters in cancer patients is unclear. Therefore, NMDA receptor 1 (NMDAR1) expression along with its clinical significance was examined in patients with oral squamous cell carcinoma (OSCC). Methods:, Eighty-one tumour specimens from OSCC patients were used to determine the NMDAR1 expression level by immunohistochemical staining. The control was obtained from a matched normal adjacent mucosa. The cases were considered to be positive if reactivity was displayed in >25% of the cells. Results:, The NMDAR1 reactivity was positive in 50 of 81 cases, while it was negative in the control. NMDAR1 expression was significantly associated with a lymph node metastasis (P = 0.008), the tumour size (P < 0.001), and the cancer stage (P = 0.034). The patients whose tumours expressed NMDAR1 had a significantly poorer survival than the patients who were NMDAR1-negative (log-rank = 6.45, d.f. = 1, P = 0.011). Conclusions:, The NMDAR1 overexpression was significantly associated with the prognosis-related factors. Therefore, it might be one of the prognostic markers of OSCC. [source] Genetic polymorphism of CCR2-64I increased the susceptibility of hepatocellular carcinoma,JOURNAL OF SURGICAL ONCOLOGY, Issue 3 2010Chao-Bin Yeh MD Abstract Background and Objectives The purpose of this study was to investigate genetic impact of monocyte chemoattractant protein-1 (MCP-1) and its receptor chemokine receptor-2 (CCR2) gene polymorphisms on the susceptibility and clinicopathological characteristics of hepatocellular carcinoma (HCC). Methods A total of 446 subjects, including 344 healthy controls and 102 patients with HCC, were recruited in this study and subjected to PCR-RFLP to estimate the impact of these two polymorphic variants on HCC. Results No relationship between MCP-1 ,2518G/A gene polymorphism and HCC risk was found among our recruited HCC patients and healthy controls. However, there was a significantly increased risk (AOR,=,1.91; 95% CI,=,1.11,3.29) of having HCC among subjects with GA heterozygotes of CCR2 V64I after adjusting for other confoundings. There was no synergistic effect between gene polymorphism and environmental risk factors, including tobacco and alcohol consumptions, as well as clinicopathological parameters of HCC for MCP-1 ,2518G/A and CCR2 V64I genes, respectively. Conclusions CCR2-64I gene polymorphism is an important factor for the susceptibility of HCC but it might not influence the clinical pathological progression of HCC, and the contribution of CCR2-64I gene polymorphism on the susceptibility of HCC could be not through the affection of liver injury-related clinical pathological characteristics. J. Surg. Oncol. 2010;102:264,270. © 2010 Wiley-Liss, Inc. [source] Hypoxia inducible factor-1, gene polymorphism G1790A and its interaction with tobacco and alcohol consumptions increase susceptibility to hepatocellular carcinoma,JOURNAL OF SURGICAL ONCOLOGY, Issue 2 2010Pei-Ching Hsiao MD Abstract Background and Objectives The aim of this study was to examine the potential associations of two hypoxia inducible factor-1, (HIF-1,) gene polymorphisms, C1772T and G1790A, with the susceptibility and clinicopathological status of hepatocellular carcinoma. Methods A total of 449 subjects, including 347 healthy controls and 102 patients with hepatocellular carcinoma, were recruited in this study and subjected to polymerase chain reaction,restriction fragment length polymorphism (PCR-RFLP) analyses to estimate the impact of these two polymorphic variants on hepatocellular carcinoma. Results G1790A heterozygotes showed a higher risk for hepatocellular carcinoma, compared with GG genotypes after adjusting for other confounders (AOR,=,3.97; 95%CI,=,1.70,9.22), indicating a significant association between hepatocellular carcinoma susceptibility and G1790A polymorphism. Moreover, results also revealed the presence of synergistic effect between gene polymorphism of HIF-1, G1790A and environmental risk factors, such as tobacco and alcohol consumptions while there was no significant association between HIF-1, gene polymorphism and clinicopathological parameters of hepatocellular carcinoma. Conclusions Genetic polymorphism at G1790A of HIF-1, is an important factor for determining the susceptibility to hepatocellular carcinoma. The interaction effects of G1790A heterozygotes to tobacco and to alcohol consumption significantly increase the risk to develop hepatocellular carcinoma. J. Surg. Oncol. 2010;102:163,169. © 2010 Wiley-Liss, Inc. [source] LAPTM4B-35 is a novel prognostic factor of hepatocellular carcinomaJOURNAL OF SURGICAL ONCOLOGY, Issue 5 2010Hua Yang MD Abstract Background LAPTM4B-35 is a 35-kDa tetra-transmembrane protein overexpressed in hepatocellular carcinoma (HCC) and promotes cell survival, proliferation, and tumorigenesis. However, the potential clinical implications of LAPTM4B-35 in HCC are still unclear. This study is aimed to investigate the correlations between LAPTM4B-35 expression and prognosis in patients with HCC. Methods Western blot and immunohistochemistry assays were used to determine the expression of LAPTM4B-35 in HCCs and their paired noncancerous liver tissues from 65 patients. The correlations of LAPTM4B-35 expression with clinicopathological parameters were assessed by Chi-square test. Patient survival was determined by Kaplan,Meier method and log-rank test. Cox regression was adopted for multivariate analysis of prognostic factors. Results LAPTM4B-35 overexpression occurred in 76.9% of HCC tissues, while only in 4.6% of noncancerous liver tissues. Overexpression of LAPTM4B-35 was significantly associated with TNM staging and invasive tumors. Patients with higher LAPTM4B-35 expression had significantly poorer overall survival (OS) and disease-free survival (DFS) (both P,<,0.001). On multivariate analysis, elevated expression of LAPTM4B-35 was found to be an independent prognostic factor for OS and DFS (P,=,0.009, 0.043, respectively). Conclusions LAPTM4B-35 overexpression is an independent prognostic factor for OS and DFS of HCC. J. Surg. Oncol. 2010; 101:363,369. © 2010 Wiley-Liss, Inc. [source] Expression of Etk/Bmx Tyrosine Kinase in Intrahepatic CholangiocarcinomaJOURNAL OF SURGICAL ONCOLOGY, Issue 5 2008Linlang Guo MD Abstract Background Epithelial and endothelial tyrosine kinase (Etk), also known as bone marrow X kinase (Bmx) plays an important role in the growth, differentiation, apoptosis, proliferation, and tumorigenicity of epithelial cells. The purpose of this study was to investigate the expression of Etk/Bmx in intrahepatic cholangiocarcinoma (ICC) and correlated the expression with clinicopathological parameters. Methods Fifty-seven cases of ICC were immunostained for Etk/Bmx, HCV NS5, PCNA, bcl-2, and NF-,B p65. Results Etk/Bmx expression was present in 19 (33.3%) of 57 ICC specimens and correlated with cell differentiation and survival rate but not closely with tumor size and lymph node metastasis. There was a significant difference of expression of either PCNA-LI or Bcl-2 between Etk/Bmx-positive and -negative cases (P,<,0.05). However, no statistically significant association was found between Etk/Bmx expression and presence of HCV-NS5 or NF-,B p65. Conclusions Our results indicate that Etk/Bmx may be involved in the development of ICC and be a predictor of poor prognosis for ICC. HCV infection and NF-,B appears unrelated to Etk/Bmx expression. J. Surg. Oncol. 2008;97:428,432. © 2008 Wiley-Liss, Inc. [source] Osteopontin expression correlates with prognostic variables and survival in clear cell renal cell carcinomaJOURNAL OF SURGICAL ONCOLOGY, Issue 4 2006Koviljka Matusan MD Abstract Background and Objectives Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including tumorigenesis and tumor cell metastasis. Recently, it has been detected in a growing number of human tumors, and assessed as a potential prognostic marker. The aim of this study was to analyze the expression of OPN in normal renal tissue and clear cell renal cell carcinomas (CRCCs), and to assess its prognostic significance. Methods The expression of OPN protein was immunohistochemically analyzed in 171 CRCCs and compared to usual clinicopathological parameters such as tumor size, nuclear grade, pathological stage, Ki-67 proliferation index, and cancer-specific survival. Results In normal renal parenchyma, the expression of OPN was seen in distal tubular epithelial cells, calcifications, and some stromal cells. The upregulation of OPN was observed in 61 CRCCs (35.7%) in the form of cytoplasmic granular staining of various intensities. Statistical analysis showed correlation of the OPN expression with tumor size (P,<,0.001), Fuhrman nuclear grade (P,<,0.001), pathological stage (P,=,0.011), and Ki-67 proliferation index (P,<,0.001). Moreover, patients with OPN-positive tumors had significantly worse prognosis in comparison to patients with tumors lacking OPN protein (P,=,0.004). Conclusion Our results suggest that overexpression of OPN is involved in the progression of CRCC. J. Surg. Oncol. 2006;94:325,331. © 2006 Wiley-Liss, Inc. [source] Meta-analysis: clinicopathological and prognostic significance of cyclooxygenase-2 expression on oesophageal squamous cell carinomaALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2009L. LI Summary Background, Cyclooxygenase-2 (COX-2) is involved in oesophageal carcinogenesis, but the clinical and prognostic significance of COX-2 expression in oesophageal squamous cell carcinoma (ESCC) remains controversial. Aim, To evaluate the clinicopathological and prognostic role of COX-2 expression in ESCC. Methods, Studies assessing clinical or prognostic significance of COX-2 expression in ESCC published until December 2008 were selected. A meta-analysis was performed to clarify the impact of COX-2 expression on clinicopathological parameters or overall survival (OS) in ESCC. Results, A total of 19 studies met the inclusion criteria, among which 17 studies were about the clinicopathological significance of COX-2 expression in ESCC, 12 studies were dealing with prognostic role of COX-2 expression in ESCC and 10 studies evaluated both of them. Overexpression of COX-2 was significantly correlated with not only the depth of invasion and TNM stage, with a combined odds ratio (OR) of 0.55 (95%CI: 0.34,0.90, Z = 2.41, P = 0.02) and 0.55 (95%CI: 0.32,0.95, Z = 2.13, P = 0.03) respectively but also the reduced OS with relative risk (RR) 1.42, 95% CI: 1.07,1.90, Z = 2.43, P = 0.02). Conclusions, COX-2 might play an important role in the progress of ESCC, overexpression of COX-2 correlates with not only the depth of invasion and TNM stage but also the reduced OS. COX-2 might be a potential therapy target for ESCC and work as a prognostic factor for ESCC patients, yet the clinicopathological and prognostic role of COX-2 in ESCC still needs further confirmation by well-designed prospective studies. [source] Possible Emergence of Drug-Resistant Variants of Babesia gibsoni in Clinical Cases Treated with Atovaquone and AzithromycinJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2009M. Sakuma Background: There is no well-established treatment strategy for Babesia gibsoni infection. A new therapeutic protocol using atovaquone (ATV) and azithromycin (AZM) has been proposed, but there is concern about the possible induction of relapse and the emergence of ATV-resistant variants after treatment. Objective: To evaluate the clinical use of combination therapy with ATV and AZM as a first-line treatment of clinical B. gibsoni infection in dogs, and to investigate the emergence of ATV-resistant variants. Animals: Eight B. gibsoni naturally infected dogs showing signs of acute onset of disease. Methods: Retrospective case study. Eight clinical cases received combination therapy with ATV and AZM at Kagoshima University Veterinary Teaching Hospital during 2007,2008, and their clinical courses and clinicopathological parameters were evaluated. In addition, alterations in the cytochrome b (CYTb) gene of B. gibsoni were analyzed by polymerase chain reaction and DNA sequencing techniques. Results: All of the dogs responded well to the treatment, with rapid improvement in their clinical condition and hematological parameters. However, 5 of the 8 dogs relapsed after treatment. Analysis of the CYTb gene strongly suggested the emergence of ATV-resistant variants after treatment. Conclusions and Clinical Importance: The combination of ATV and AZM can be used as a first-line treatment for dogs with babesiosis, but relapses occur. Attention should be paid to the possible in vivo selection of drug-resistant variants. [source] Epigenetic inactivation of HOXA5 and MSH2 gene in clear cell renal cell carcinomaPATHOLOGY INTERNATIONAL, Issue 10 2010Koo Han Yoo The high-throughput method using microarray is an easy and fast way to analyze the methylation status of hundreds of preselected genes and to screen them for signatures in methylation. The aim of our study is to detect hypermethylated genes and to analyze the association between methylation status and clinicopathological parameters of clear cell renal cell carcinoma. The genetic substrate included 62 cancer tissues and 62 matched adjacent normal kidney tissues. We adapted the GoldenGate genotyping assay to determine the methylation state of 1505 specific CpG sites in 807 genes. We identified two genes (HOXA5 and MSH2) with ,-value differences of more than 0.3 between cancer and normal tissues. The high methylation group in HOXA5 had high Fuhrman's nuclear grade (P= 0.041). Other data in HOXA5 and MSH2 were not significant with methylation status (P > 0.05). Survival curve of the high methylation group in HOXA5 was slightly lower than that of the low methylation group. However, the statistical significances of overall survival in HOXA5 and MSH2 were low (P > 0.05). We report the hypermethylation of two genes in clear cell renal cell carcinoma. The data we obtained could provide the basis for a diagnostic test pathological assessment, or prognosis in clear cell renal cell carcinoma. [source] Increased staining for phosphorylated AKT and nuclear factor-,B p65 and their relationship with prognosis in epithelial ovarian cancerPATHOLOGY INTERNATIONAL, Issue 12 2008Rui-Xia Guo AKT plays an important role in malignant behavior of tumors. The purpose of the present study was to determine the expression of phosphorylated AKT (P-AKT) and nuclear factor-,B (NF-,B) p65 and their association with clinicopathological parameters and prognosis in epithelial ovarian tumor. On immunohistochemistry 115 samples of ovarian tissue that included 68 specimens of epithelial ovarian cancer, 12 of borderline tumor, 24 of epithelial benign tumor and 11 of normal ovary, were evaluated. Sixty-three patients with ovarian cancer were followed up from 7 to 68 months. The positive expression rate of P-AKT and NF-,B p65 were higher in epithelial ovarian cancer than in normal ovarian tissue (P < 0.01). Elevated P-AKT or NF-,B p65 expression was significantly correlated with late clinical stage (P < 0.05 and P < 0.01) and poor histological differentiation (both P < 0.01). P-AKT expression was significantly correlated with NF-,B p65 immunostaining (, = 0.272, P < 0.05). Elevated expression of P-AKT was negatively correlated with the survival of ovarian cancer patients, but it was not an independent prognostic factor after multivariate analysis. Overexpression of P-AKT and NF-,B p65 were involved in the carcinogenesis and metastasis of ovarian cancer. P-AKT might contribute to the malignant transformation through NF-,Bp65 upregulation. [source] Expression of connective tissue growth factor is in agreement with the expression of VEGF, VEGF-C, -D and associated with shorter survival in gastric cancerPATHOLOGY INTERNATIONAL, Issue 11 2007Luying Liu Connective tissue growth factor (CTGF) is believed to be a multifunctional signaling modulator involved in a wide variety of biological or pathological processes including carcinogenesis. The role of CTGF in gastric cancer (GC) has not been reported so far. In the present study the expression of CTGF, vascular endothelial growth factor (VEGF), VEGF-C and VEGF-D on immunohistochemistry in GC and the correlation between the expression of CTGF and VEGF, VEGF-C, VEGF-D were examined, along with the correlation between the expression of CTGF and clinicopathological parameters, as well as survival of the patients with GC. The expression of CTGF was significantly in agreement with expression of VEGF, VEGF-C and VEGF-D (, and P, respectively: 0.538, P < 0.001; 0.502, P < 0.001; 0.558, P < 0.001). High CTGF expression was significantly associated with lymph nodes metastasis (P = 0.038) and lower postoperative 5 year overall survival rates (23.9%) compared with those patients with low CTGF expression (48.4%, P = 0.0035). The present findings suggest that CTGF is a useful prognostic marker for GC. High CTGF expression is associated with the risk of lymph nodes metastasis and a poor survival time in GC. [source] Overexpression of serine,threonine receptor kinase-associated protein in colorectal cancersPATHOLOGY INTERNATIONAL, Issue 4 2007Chang Jae Kim Transforming growth factor-, (TGF-,) regulates many cellular processes, including cellular proliferation and differentiation. Disruption of the TGF-, signaling pathway can lead to cancer. Serine,threonine receptor kinase-associated protein (STRAP), an inhibitor of TGF-, signaling, is an important regulator of cell proliferation. Here, in order to investigate the roles of STRAP in colorectal carcinogenesis, the expression of the STRAP protein was investigated in 59 colonic adenomas and 123 colorectal cancers by immunohistochemistry. Upregulation of STRAP protein was observed in 30 (50.8%) of 59 adenomas and 87 (70.7%) of 123 cancers, respectively. Statistically, overexpression of STRAP protein was not associated with clinicopathological parameters and 5 year survival (P > 0.05). Interestingly, significant association was observed between STRAP and Ki-67 positivity (P < 0.05), suggesting that STRAP contributes to an increased proliferate potential of tumor cells. These results indicate that upregulation of STRAP might play a role in tumor development as an early event for colorectal cancers. [source] | |||||||||||||||||||||||||||||||