Bladder Transitional Cell Carcinoma Tissues Research Articles

Expression and correlation of Bmi-1, AEG-1 and FHIT in bladder transitional cell carcinoma.

BackgroundTo explore the expression and correlation of B-cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1), astrocyte elevated gene-1 (AEG-1) and fragile histidine triad (FHIT) in bladder transitional cell carcinoma (BTCC).MethodsForty-six tissue samples were obtained from patients diagnosed with primary bladder cancer during the first radical cystectomy between June 2010 and January 2014. The expression of Bmi-1, AEG-1 and FHIT in normal tissues and BTCC tissues in different histological cell types, clinical pathological stages and lymph node metastatic status were evaluated by quantitative real time polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry. Relationships between Bmi-1, AEG-1 and FHIT were determined using linear correlation coefficient.ResultsThe results of qRT-PCR showed the relative expression of Bmi-1 and AEG-1 were higher and the expression of FHIT was lower in BTCC tissues than those in normal tissues, whether in different histological cell types, clinical pathological stages or lymph node metastatic status (P<0.05). Similarly, the up-regulated expression of Bmi-1 and AEG-1 and down-regulated expression of FHIT in BTCC tissues were observed by the Western blot and immunohistochemistry compared with normal tissues (P<0.05). Linear correlation analysis showed the expression of Bmi-1 was positively correlated with AEG-1 (r>0.90, P<0.01), which was negatively correlated with the expression of FHIT, respectively (r=−0.84, P<0.05).ConclusionsThe study demonstrated the up-regulated expression of Bmi-1 and AEG-1 and the down-regulated expression of FHIT in BTCC tissues. The interaction of Bmi-1, AEG-1 and FHIT may involve in the tumorigenesis, progression and invasion of BTCC through NF-κB/MMP-9 pathway.

The expression of apolipoproteina1 and its correlation with infiltration of urologic neoplasm.

BackgroundTo explore the differential expression of apolipoproteinA1 (APOA1) in urologic neoplasm patient compared with controls, as well as investigates whether APOA1 correlated with infiltration of urologic neoplasm.MethodsA total of 59 tissue sections of surgically-resected urologic neoplasm and 6 cases of normal tissue sections were collected. Fourteen cases of urine samples from transitional cell carcinoma patients and 6 cases urine samples from controls were also applied in this experiment. We also selected 6 cases of fresh bladder transitional cell carcinoma tissues. The urologic neoplasm tissue sections were classified into infiltration and non-infiltration urologic neoplasm groups. The expressions of APOA1 between urologic neoplasm and normal control were detected by Western blot, Immunohistochemistry and qRT-PCR. The method of Immunohistochemistry was applied to examine the differences of APOA1 expression between infiltration and non-infiltration urologic neoplasm tissue section groups.ResultsCompared with none expression in normal controls, APOA1 was exhibited higher level in urologic neoplasm patient’s urine and fresh bladder transitional cell carcinoma tissues (P<0.05). There were statistical differences of APOA1 between infiltration and non-infiltration urologic neoplasm tissue section groups. APOA1 expressions were found to be up-regulated in the infiltration neoplasm tissue sections compared to non-infiltration group (P<0.001).ConclusionsAPOA1 could act as a valuable biomarker for predicting the occurrence and development of urologic neoplasm.

Corrigendum] MicroRNA‑497 inhibits the proliferation, migration and invasion of human bladder transitional cell carcinoma cells by targeting E2F3.

Subsequently to the publication of the above article, the authors have realized that Fig.4E in their paper contained errors. The image selected to represent the experiment showing the UM‑UC‑3 cells of the siE2F3 group (0h) was chosen incorrectly during the figure compilation process. A corrected version of Fig.4 is shown opposite. Note that this error affected neither the interpretation of the data nor the reported conclusions of this work, and all the authors agree to this Corrigendum. The authors apologize to the Editor and the readership of the Journal for this unintentional error, and for any inconvenience caused. [the original article was published in Oncology Reports 36: 1293‑1300, 2016; DOI: 10.3892/or.2016.4923].

Overexpression of Epidermal Growth Factor Receptor (EGFR) and HER-2 in Bladder Carcinoma and Its Association with Patients' Clinical Features.

BackgroundThe aim of this study was to determine the expression of EGFR/HER-2 and investigate their association with patients’ clinical features in bladder transitional cell carcinoma (BTCC).Material/MethodsImmunohistochemistry was utilized in our study to explore the expression of EGFR/HER-2 of 56 human bladder cancer samples and 10 normal bladder samples.ResultsEGFR and HER-2 expressions were both significantly higher in bladder transitional cell carcinoma (BTCC) than that in non-cancer bladder samples; the EGFR positivity rate was 55.4% among BTCC samples and 37.5% for HER-2a. A statistically significant correlation was also present between the increasing EGFR or HER-2 expression levels and the clinical stages, pathologic grades, and tumor recurrence. The expression level of EGFR increased along with higher clinical stages and pathologic grades of BTCC, and the obviously increased expression of HER-2 was statistically associated with clinical stages and tumor recurrence. In addition, the expression level of HER-2 increased along with the higher clinical stage of BTCC. EGFR expression and HER-2 levels were positively associated in BTCC samples.ConclusionsOur findings demonstrate that high EGFR and HER-2 expressions are dramatically increased in the BTCC tissues and are closely related to the clinical stages, pathologic grades, and tumor recurrence. Therefore, the evaluation of EGFR and HER-2 expression in BTCC may contribute to identifying patients who are at increased risk of disease progression and recurrence.

HMGN5 expression in bladder cancer tissue and its role on prognosis.

High mobility group protein N5 subtype (HMGN5) is overexpressed in bladder cancer tissue, while its specific mechanism in bladder cancer oncogenesis has not been fully elucidated. This study intends to investigate the impact of HMGN5 on clinical staging and prognosis of bladder cancer. A total of 26 cases of patients with bladder transitional cell carcinoma (BTCC) received transurethral resection (TUR-BT) in our hospital between March 2015 and February 2016. Para-carcinoma tissue at 5 cm away from cancer tissue was selected as normal control. The expressions of HMGN5 mRNA and protein in different clinical stages were tested by Real-time PCR and Western blot. The relationship between HMGN5 expression and clinical stage along with prognosis was analyzed. HMGN5 mRNA was significantly elevated in BTCC tissue compared with that in para-carcinoma tissue (p < 0.05). HMGN5 mRNA level was gradually upregulated following BTCC upstage according to UICC-TNM stage and WHO stage. The level of HMGN5 protein showed similar changes with mRNA. Follow-up results demonstrated that patients with high HMGN5 level have more tendency of occurrence. HMGN5 protein level has an important influence on BTCC clinicopathological staging and prognosis. This investigation provides theoretical basis the future therapy of bladder cancer.

Wild-type p53-induced phosphatase 1 is a prognostic marker and therapeutic target in bladder transitional cell carcinoma

Wild-type p53-induced phosphatase (Wip1) is an established oncogene and is associated with development of multiple forms of human cancer. However, the expression and role of Wip1 in human bladder transitional cell carcinoma (TCC) remains to be elucidated. In the present study, immunohistochemistry demonstrated that Wip1 was overexpressed in bladder TCC tissues compared with corresponding normal bladder tissues in 106 bladder TCC cases (P<0.0001). Furthermore, high expression levels of Wip1 were significantly associated with increasing tumor size (P=0.002), pathological grade (P=0.025), clinical T stage (P=0.001) and lymph nodal metastasis (P=0.003). Kaplan-Meier survival analysis identified that patients with high Wip1 expression levels exhibited a lower overall survival time (P<0.0001), and Cox proportional hazards regression model analysis demonstrated that Wip1 expression was an independent prognostic factor in patients with bladder TCC (P=0.025). In addition, downregulation of Wip1 expression by transfection with small interfering RNA in bladder cancer cells inhibited cell proliferation, invasion and migration (P<0.05), along with the upregulation of p53 protein levels (P<0.05). These findings suggest that Wip1 may function as a potential prognostic marker and therapeutic target in bladder cancer.

MicroRNA-497 inhibits the proliferation, migration and invasion of human bladder transitional cell carcinoma cells by targeting E2F3.

Accumulating evidence indicates that microRNAs (miRNAs) play critical roles in regulating cellular processes, such as cell growth and apoptosis, as well as cancer progression and metastasis. Low expression of miR-497 has been observed in breast, colorectal and cervical cancers. Human bladder transitional cell carcinoma (BTCC) progression typically follows a complex cascade from primary malignancy to distant metastasis, but whether the aberrant expression of miR-497 in BTCC is associated with malignancy, metastasis or prognosis remains unknown. In the present study, we found that miR-497 was markedly downregulated in BTCC tissue samples when compared with that noted in adjacent normal tissues, and low expression of miR-497 was correlated with poor prognosis in BTCC patients. We also found that overexpression of miR-497 inhibited the proliferation, migration and invasion of bladder cancer cells by downregulating E2F3 (an miR-497 target gene) mRNA and protein and that siRNA against E2F3 inhibited cell proliferation, migration and invasion, which was similar to the effect of miR-497 overexpression in the BTCC cells. Our experimental data indicated that miR-497 mediates the invitro proliferation, migration and invasion of BTCC cells. Together, these results suggest that miR-497 may represent a novel prognostic indicator, a biomarker for the early detection of metastasis and a target for gene therapy of BTCC.

Association of thymosin β4 expression with clinicopathological parameters and clinical outcomes of bladder cancer patients.

The clinical significance of thymosin β4 (Tβ4) expression in bladder transitional cell carcinoma (BTCC) remains unclear. The present study assessed the relationship between the expression of Tβ4 protein and the clinicopathological features, as well as the prognosis of bladder cancer patients. Tβ4 protein expression in 24 normal bladder and 138 primary BTCC tissue specimens was detected by immunohistochemistry, and the association of this expression with BTCC clinicopathological features and recurrence as well as patient survival was analyzed. Tβ4 expression was significantly stronger in BTCC patients than in normal volunteers. The expression of Tβ4 was significantly associated with differentiation capability, tumor stage and lymph node metastasis (P = 0.025, 0.043, and 0.039, respectively). Moreover, Tβ4 expression was positively correlated with integrin-linked kinase (ILK) and β-catenin expression (P = 0.042, 0.031, respectively) and inversely correlated with E-cadherin expression (P = 0.022). In the present cohort of bladder cancer patients, Tβ4 expression was found to be a predictor of poor survival (P < 0.05); however, high Tβ4 expression exhibited unfavorable prognostic value for recurrence. These data suggested that Tβ4 is correlated with the pathogenesis of BTCC. In addition, the patients with higher Tβ4 expression had a shorter survival.

Expression of brain‑specific angiogenesis inhibitor‑1 and association with p53, microvessel density and vascular endothelial growth factor in the tissue of human bladder transitional cell carcinoma.

The aim of the present study was to investigate the expression levels of brain‑specific angiogenesis inhibitor‑1 (BAI‑1) in bladder transitional cell carcinoma (BTCC) at different stages and the mechanism by which it inhibits tumor endothelial cell proliferation. Normal bladder mucosa biopsy specimens were obtained as the control group, and human BTCC biopsy specimens were used as the study group. Immunohistochemical assays were used to detect the expression levels of BAI‑1, vascular endothelial growth factor (VEGF) and mutant p53, in addition to microvessel density (MVD) in the tissues. Western blotting was used to analyze the differential expression of BAI‑1 in the two samples. Statistical analysis was performed, which indicated that BAI‑1 expression levels in the normal bladder mucosa group were significantly higher than those in the BTCC group and were associated with clinical staging. BAI‑1 levels in the T1 stage BTCC tissues were higher than those in the T2‑4 stage BTCC tissues (P<0.05). BAI‑1 expression levels were negatively correlated with those of VEGF (r=‑0.661, P<0.001), mutant p53 (r=‑0.406, P=0.002) and with the MVD (r=‑0.675, P<0.001). BAI‑1 may be involved in the negative regulation of BTCC microvascular proliferation, and its expression may be associated with a reduction in p53 mutations.

Relationship between lipid metabolism regulation by microRNA-107 and bladder transitional epithelial cancer clinical progress

Objective To investigate the expression level of carbohydrate response element binding protein(Ch REBP)and fatty acid synthase(FASN)in the different clinical stages of bladder transitional cell carcinoma(BTCC), and explore the relationship between microRNA(miRNA, miR)-107 and Snail1 pathway with clinicopathological features of BTCC. Methods Forty-eight cases of BTCC specimens surgically resected were selected.For each specimen, the cancerous tissue, peri-cancer and its remote normal mucosa were obtained. The expression of miR-107, Snail1, ChREBP, and FASN in resected cancer tissues was detected by reverse transcriptase-polymerase chain reaction(RT-PCR), and its relationship with clinicopathologic features of BTCC was analyzed. Results (1) The expression rate of Ch REBP and FASN was significantly higher in BTCC tissues than in normal tissues(12. 278±4. 035 vs.8. 442±7. 658, and 13. 536±4. 776 vs.9. 183± 6. 112,P 0. 05).miR-107 was positively related to ChREBP and FASN expression in BTCC tissues, and miR-107 and Snail1 expression was inversely correlated to ChREBP and FASN in peri-cancer tissues(67. 5% vs. 32. 4%, and 73. 0% vs.27. 0%,P< 0. 05). Conclusion The miR-107 was related with the pathological grading of BTCC, which may change the traditional metabolic pathway to mediate the occurrence and development of bladder cancer through the regulation of Ch REBP and FASN. Key words: microRNA-107; Carbohydrate response element binding protein; Fatty acid synthase; Bladder transitional cell carcinoma; Epithelial-mesenchymal transition

The expression and clinical significance of microRNA-107 in bladder transitional cell carcinoma

Objective To detect the expression level of microRNA(miR)- 107 in the different clinical stages of bladder transitional cell carcinoma(BTCC), and explore the relationship between miR- 107 pathway and clinicopathological features of BTCC. Methods Fifty- six BTCC specimens surgically resected were selected.For each specimen, the cancerous tissue and its remote normal mucosa were analyzed and compared.The expression of miR- 107, let- 7, Dicer, Ras/high mobility group A2(HMGA2), and zinc-finger E-box binding homeobox 1(ZEB1)/zinc-finger E-box binding homeobox 2(ZEB2)in the resected cancer tissues was detected by using real- time quantitative polymerase chain reaction(Real- time PCR), Western blotting and immunohistochemistry, and their correlation with clinicopathological features was analyzed. Results (1) The expression rate of miR-107 was significantly higher in BTCC tissues than in normal tissues(14.983±6.215 vs.9.124±5.595), and that in deeply infiltrating group was significantly higher than that in superficially infiltrating group (15.183±6.035 vs.11.728±5.472, and 14.663±5.215 vs.10.983±5.674,P 0.05).Ras/ HMGA2, let- 7 downstream regulatory factors, were significantly higher in BTCC than in normal tissues(89.3% vs.23.2%, and 80.3% vs.28.6%,P< 0.05). The expression of let- 7, and Dicer in BTCC tissues was significantly lower than in normal bladder epithelium (P< 0.05);(2) miR- 107 expression was inversely correlated to let- 7 and Dicer. Conclusion The miR- 107 was related with the clinical stages of BTCC through the regulation of Dicer and let- 7 pathways, which mediates the occurrence and development of bladder cancer. Key words: Micro RNA- 107; Dicer; Bladder transitional cell carcinoma; Epithelialmesenchymal transition

SATB1 overexpression regulates the development and progression in bladder cancer through EMT.

The global gene regulator Special AT-rich sequence-binding protein-1 (SATB1) has been reported to induce EMT-like changes and be associated with poor clinical outcome in several cancers. This study aims to evaluate whether SATB1 affects the biological behaviors of bladder transitional cell carcinoma (BTCC) and further elucidate if this effect works through an epithelial-mesenchymal transition (EMT) pathway. The expression of SATB1, E-cadherin (epithelial markers), vimentin (mesenchymal markers) in BTCC tissues and adjacent noncancerous tissues, as well as in two cell lines of bladder cancer were investigated. Whether the SATB1 expression is associated with clinicopathological factors or not was statistically analyzed. Cell invasion and migration, cell cycle, cell proliferation and apoptosis were evaluated in SATB1 knockdown and overexpressed cell lines. Our results showed that the expression of SATB1 was remarkably up-regulated both in BTCC tissues and in bladder cancer cell lines with high potential of metastasis. The results were also associated with EMT markers and poor prognosis of BTCC patients. Moreover, SATB1 induced EMT processes through downregulation of E-cadherin, upregulation of E-cadherin repressors (Snail, Slug and vimentin). SATB1 also promoted cell cycle progression, cell proliferation, cell invasion and cell migration, but did not alter cell survival. In conclusion, our results suggest that SATB1 plays a crucial role in the progression of bladder cancer by regulating genes controlling EMT processes. Further, it may be a novel therapeutic target for aggressive bladder cancers.

Quantitation of rare circulating tumor cells by folate receptor α ligand-targeted PCR in bladder transitional cell carcinoma and its potential diagnostic significance.

Numerous attempts for detection of circulating tumor cells (CTC) have been made to develop reliable assays for early diagnosis of cancers. In this study, we validated the application of folate receptor α (FRα) as the tumor marker to detect CTC through tumor-specific ligand PCR (LT-PCR) and assessed its utility for diagnosis of bladder transitional cell carcinoma (TCC). Immunohistochemistry for FRα was performed on ten bladder TCC tissues. Enzyme-linked immunosorbent assay (ELISA) for FRα was performed on both urine and serum specimens from bladder TCC patients (n = 64 and n = 20, respectively) and healthy volunteers (n = 20 and n = 23, respectively). Western blot analysis and qRT-PCR were performed to confirm the expression of FRα in bladder TCC cells. CTC values in 3-mL peripheral blood were measured in 57 bladder TCC patients, 48 healthy volunteers, and 15 subjects with benign urologic pathologies by the folate receptor α ligand-targeted PCR. We found that FRα protein was overexpressed in both bladder TCC cells and tissues. The levels of FRα mRNA were also much higher in bladder cancer cell lines 5637 and SW780 than those of leukocyte. Values of FRα were higher in both serum and urine specimens of bladder TCC patients than those of control. CTC values were also higher in 3-mL peripheral blood of bladder TCC patients than those of control (median 26.5 Cu/3 mL vs 14.0 Cu/3 mL). Area under the receiver operating characteristic (ROC) curve for bladder TCC detection was 0.819, 95 % CI (0.738-0.883). At the cutoff value of 15.43 Cu/3 mL, the sensitivity and the specificity for detecting bladder cancer are 82.14 and 61.9 %, respectively. We concluded that quantitation of CTCs through FRα ligand-PCR could be a promising method for noninvasive diagnosis of bladder TCC.

Down-regulated microRNA-101 in bladder transitional cell carcinoma is associated with poor prognosis.

BackgroundDown-regulation of microRNA-101 (miR-101) expression has been linked to bladder transitional cell carcinoma (BTCC) development. However, the relationship between the expression of miR-101 in BTCC and a patient’s prognosis has not yet been studied. Thus, we attempted to explore the correlation of miR-101 and clinicopathological factors of BTCC patients, and evaluate the impact of miR-101 on prognosis of BTCC.Material/MethodsIn 88 samples of BTCC (n=72) and normal tissues (n=16), the expressions of miR-101 were detected by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). The relationship of miR-101 and clinicopathological factors in BTCC was analyzed statistically. Survival analysis was performed to assess the prognostic significance of miR-101.ResultsDown-regulation of miR-101 was found in BTCC tissues, compared with normal tissues (P<0.05). MiR-101 expression was significantly associated with tumor diameter, tumor stage, tumor grade, lymph node involvement, and lymph node metastasis (all P<0.05). Low-level expression of miR-101 was significantly correlated with shortened survival time (P<0.01). Multivariate Cox regression analysis revealed this significant prognostic impact was independent of other clinicopathologic factors (P<0.01).ConclusionsOur results suggest that the expression of miR-101 is down-regulated in BTCC, which consequently favored tumor progression. MiR-101 may play an important role as a diagnostic and prognostic marker in BTCC.

CXCR4 Expression in Bladder Transitional Cell Carcinoma and Its Relationship with Clinicopathological Features

Objective: To elucidate the role of CXCR4 in the metastasis of bladder transitional cell carcinoma (BTCC) by examining CXCR4 expression in BTCC tissue and its correlation with clinicopathological features. Methods: The expression of CXCR4 was assessed in bladder tissues from 70 BTCC patients and 18 normal controls, respectively, using immunohistochemistry. The correlation of CXCR4 expression with lymph node metastasis was also examined by determining the lymphatic vessel density (LVD). Results: Overexpression of CXCR4 was detected in 58/70 (82.9%) BTCC tissues, whereas only in 3/18 (16.7%) normal bladder tissues. The expression was significantly higher in BTCC than that in normal controls (p < 0.01). CXCR4 expression level was closely associated with tumor size, pathological grades, clinical stages, and pelvic lymph node metastasis (p < 0.05). Multivariate analysis indicated that CXCR4 expression and lymph node metastasis were independent predictors for disease-free survival (both p < 0.05). The disease-free survival rate among the patients with high CXCR4 expression level was remarkably lower than that among the patients with no or low level expression (p < 0.01). Conclusion: Highly expressed in BTCC tissues, CXCR4 may play a critical role in the metastasis of BTCC, and the expression level in biopsy specimens might be a good indicator of lymph node metastasis.

Correlation between transcription factor forkhead box protein Q1 and epithelial-mesenchymal transition in human bladder transitional cell carcinoma

Objective To investigate the relationship between transcription factor forkhead box protein Q1 (FOXQ1) and epithelial mesenchymal transition (EMT) in bladder transitional cell carcinoma (BTCC),and the association between FOXQ1 and clinicopathologic features.Methods Sixty-five BTCC specimens surgically resected were selected.For each specimen,the cancerous tissue,peri-cancerous tissue and the remote normal mucosa were analyzed and compared.The expression of FOXQ1,transforming growth factor (TGF)-βl,E-cadherin and Vimentin genes in resected cancer tissues was detected by using reverse transcription-polymerase chain reaction (RT-PCR),Western blotting and immunohistochemistry,and their association with clinicopathologic data was analyzed.Results (1) The expression rate of FOXQ1 was significantly higher in BTCC tissues than in normal tissues (89.2％ vs 13.8％,P ＜0.05),and that in deeply infiltrating group was significantly higher than that in superficially infiltrating group (97.3％ vs 78.6％,P ＜0.05).The level of TGF-β1 was significantly higher in BTCC tissues than in normal tissues (76.9％ vs 26.2％,P ＜0.05).The expression level of E-cadherin in BTCC tissues was significantly lowered in comparison with that in normal bladder epithelium (27.7％ vs 89.2％,P ＜0.05).The expression rate of Vimentin was higher in BTCC tissues than in normal tissues (83.1％ vs 20.0％,P ＜ 0.05) ; (2)The expression of FOXQ1 serving as one new positive control factor of EMT was inversely correlated to Ecadherin,but positively to TGF-β1 and Vimentin.Conclusion FOXQ1 is related to the differentiation and metastasis of BTCC,and may induce EMT to promote BTCC metastasis. Key words: Epithelial mesenchymal transition; Bladder transitional cell carcinoma; Transcription factor; Forkhead box protein Q1

Downregulation of CDH13 Expression Promotes Invasiveness of Bladder Transitional Cell Carcinoma

Objective: To investigate the association of downregulated CDH13 expression with invasiveness of bladder transitional cell carcinoma (TCC). Materials and Methods: CDH13 and matrix metalloproteinase-2 (MMP2) expression was detected in 23 normal bladder epithelial tissues and 71 bladder TCC tissues. RNA interference was used to inhibit CDH13 expression in bladder TCC 5637 cells and then analyzed its effects on migration, invasion, adhesion, and proliferation of 5637 cells, as well as MMP2 expression in 5637 cells. Results: The CDH13 expression in bladder TCC tissues was significantly lower than that in normal bladder epithelial tissues. Moreover, the expression of CDH13 from the muscle-invasive group was significantly lower than that from the non-muscle-invasive group. In addition, the MMP2 expression was increased in bladder TCC, especially in muscle-invasive tumors. After the transfection of CDH13 siRNA into 5637 cells, CDH13 expression was significantly decreased, and the migration, invasion, adhesion of 5637 cells, as well as MMP2 expression in 5637 cells was significantly promoted compared with blank and negative controls. Conclusions: Downregulated expression of CDH13 is associated with increased invasion of bladder TCC, and may be due to the enhancement of cell-extracellular matrix adhesion and increased MMP2 expression.

Expressions of PTEN and MDM2 in bladder transitional cell carcinoma and their clinical significance

Objective To investigate the expressions of PTEN and MDM2 in bladder transitional cell carcinoma (BTCC) and their clinical significance.Methods The expressions of PTEN and MDM2 were detected by tissue immunohistochemistry test (SP method) in BTCC (n =80) and normal bladder tissues (n =20).The relationship between PTEN and MDM2 as well as their correlations with clinical pathological features were analyzed.Results The positive rate of PTEN in different pathological grading (G1,G2,G3)and clinical staging [superficial (Tis ～ T1),infiltration (T2 ～ T4)] was (86.20％,74.07％,37.50％ ;80.00％,46.67％),respectively,with a significant difference (x2 =15.004,P ＜ 0.01 ; x2 =9.497,P ＜0.01).The positive rate of MDM2 in different pathological grading(G1,G2,G3) and clinical staging [superficial (Tis ～ T1),infiltration (T2 ～ T4)] was (82.75％,55.55％,37.50％ ; 70.00％,43.35％),respectively,with a significant differcnce(x2 =11.543,P ＜ 0.01 ; x2 =5.556,P ＜ 0.05).The expression of PTEN was negatively correlated with that of MDM2 in BTCC (r =-0.611,P ＜ 0.05).Conclusions Expressions of PTEN and MDM2 might be involved in the BTCC pathogenesis.The combined detection of PTEN and MDM2 might be of great value in the prediction of tumor behavior and prognosis. Key words: Urinary bladder neoplasms/pathology ; Urinary bladder neoplasms/metabolism ; Genes, tumor suppressor; Gene expression; Proto-oncogene proteins

Tumor suppressor gene methylation in tissue and urine specimens of bladder transitional cell carcinoma

Objective To investigate abnormal promoter methylation status of death-associated protein kinase(DAPK),retinoic acid receptorβ(RARβ),Hyperplastic polyps protein(HPP1) and integrin alpha-4 precursor (ITGA4) genes,and the diagnostic value for bladder transitional cell carcinoma (BTCC).Methods Methylation-specific polymerase chain reaction (MSP) was used to detect the methylation status of DAPK,RARβ,HPP1 and ITGA4 genes in tissue and urine specimens of 112 patients with BTCC.Results The methylation rate of DAPK,RARβ,HPP1 and ITGA4 in BTCC tissue was 29.4％,91.0％,75.0％ and 48.2％ respectively,and that in urine sediment cells was 26.7％,87.5％,69.6％ and 27.6％ respectively.Aberrant methylation rate of DAPK,HPP1 and RARβ genes in BTCC was significantly different from that in the glandular cystitis (P ＜ 0.05).There was no significant difference in the methylation rate of ITGA4 between BTCC and and cystitis glandularis (P ＞ 0.05).Conclusion Aberrant methylation status of HPP1,DAPK1,and RARβ is closely related with incidence of bladder cancer. Key words: Bladder carcinoma; Urine sediment cells; Tumor suppressor gene; Methylation

Expression of Survivin and leucine-rich and immunoglobulin-like domain 2 in human bladder transitional cell carcinoma and its clinical application

Objective To investigale the expression of Survivin and leucine-rich and immunoglobulin-like domain 2 (LRIG2) in bladder transitional cell carcinoma ( BTCC ),and their association with clinicopathologic features.Methods Seventy-two BTCC specimens surgically resected were selected.For each specimen,the cancerous tissue,peri-cancer tissue and its remote normal mucosa were analyzed and compared.Immunohistochemistv was used to detect the expression of Survivin and LRIG2 in 72 cases of BTCC tissues.Results The immunohistochemisty revealed that the expression of Sruvivin in BTCC was much higher than that in peri-cancer tissues ( 90.28％ vs.33.33 ％,P ＜ 0.05 ),but no expression was detectable in normal bladder tissues.Among the pathological grades of G1,G2 and G3,the positive rate of Survivin respectively was 72.22％,90.48％ and 100.00％.In the clinical stages of Ta-Tis and T1-T2,the positive rate of Survivin respectively was 81.25％ and 97.50％,and in the two groups with lymphatic metastasis and negative lymphatic metastasis,it respectively was 96.00％ and 85.11％. Moreover,with the advancing grades and clinical stages and appearances of lymph node metastasis,the expression of Survivin was increased gradually.There were significant diffrences in each group ( P ＜ 0.05 ).The expression rate of LRIG2 was significantly lower in BTCC tissues than in peri-cancer tissues and normal tissues (30.56％,66.67％ and 87.50％ respectively).Among the pathological grades of G1,G2 and G3,the positive rate of LRIG2 respectively was 33.33％,19.05％,and 9.38％.With the advancing grades and clinical stages and appearances of lymph node metastasis,the expression of LRIG2 was decreased gradually,and there were significant differences in each group (P ＜ 0.05).Moreover,the expression of Survivin was inversely correlated to LRIG2. Conclusion The expression of Survivin and LRIG2 is related to the clinicopathologic features of BTCC with differentiation and metastasis.The over-expression of Survivin and genetic mutation or missing of LRIG2 may play an important role in carcinogenesis and progress of BTCC.Detection of Survivin and LRIG2 protein will be helpful to the early diagnosis and treatment of BTCC and evaluate its biologic behaviors. Key words: Survivin; Leucine-rich and immunoglobulin-like domain 2; Bladder transitional cell carcinoma