Detection of survivin expression in bladder cancer and renal cell carcinoma using specific monoclonal antibodies.

Survivin, which is highly expressed in the majority of tumors, but not in most normal adult tissues, has been identified to have significant clinical applications. In the present study, using survivin­specific monoclonal antibodies (mAbs), we aimed to establish methods for detecting the expression of survivin in cancer cell lines, serum samples, urine samples and cancer tissues from patients with bladder cancer (BCa) and renal cell carcinoma (RCC), and to evaluate the efficacy of survivin as a tumor marker in the surveillance of BCa and RCC. First, mAbs were labeled with horseradish peroxidase (HRP), and a sandwich enzyme­linked immunosorbent assay (ELISA) with mAbs and HRP­conjugated mAbs was developed to detect survivin expression in serum and urine samples from BCa and RCC patients, with samples from healthy controls (HCs) used for comparison. The HRP­conjugated mAbs were also used to detect survivin expression in cancer cell lines by western blotting. Survivin expression in cancer tissues from BCa patients was also evaluated by immunohistochemistry. The results showed that the sandwich ELISA was successfully established, and significantly higher expression of survivin was subsequently detected in BCa and RCC patients as compared with HCs in both urinary and serum samples (P<0.05), and was more pronounced in urine. The HRP­mAbs could recognize survivin in cancer cell lines. Western blotting and immunohistochemistry results confirmed survivin expression in the 5637 BCa cell line, as well as BCa tissues. In addition, the expressions of survivin in BCa tissues, urine and serum were consistent in our study. In conclusion, the sandwich ELISA successfully established in the present study was of high sensitivity and specificity in the detection of survivin expression. The results also indicated that survivin is a potential tumor marker for the surveillance of BCa and RCC.

Evaluation of a New Survivin ELISA and UBC® Rapid for the Detection of Bladder Cancer in Urine.

Urine-based biomarkers for non-invasive diagnosis of bladder cancer are urgently needed. No single marker with sufficient sensitivity and specificity has been described so far. Thus, a combination of markers appears to be a promising approach. The aim of this case-control study was to evaluate the performance of an in-house developed enzyme-linked immunosorbent assay (ELISA) for survivin, the UBC®Rapid test, and the combination of both assays. A total of 290 patients were recruited. Due to prior bladder cancer, 46 patients were excluded. Urine samples were available from 111 patients with bladder cancer and 133 clinical controls without urologic diseases. Antibodies generated from recombinant survivin were utilized to develop a sandwich ELISA. The ELISA and the UBC®Rapid test were applied to all urine samples. Receiver operating characteristic (ROC) analysis was used to evaluate marker performance. The survivin ELISA exhibited a sensitivity of 35% with a specificity of 98%. The UBC®Rapid test showed a sensitivity of 56% and a specificity of 96%. Combination of both assays increased the sensitivity to 66% with a specificity of 95%. For high-grade tumors, the combination showed a sensitivity of 82% and a specificity of 95%. The new survivin ELISA and the UBC®Rapid test are both able to detect bladder cancer, especially high-grade tumors. However, the performance of each individual marker is moderate and efforts to improve the survivin assay should be pursued. A combination of both assays confirmed the benefit of using marker panels. The results need further testing in a prospective study and with a high-risk population.

Survivin splice variants and their diagnostic significance.

Survivin plays a crucial role in cell division particularly during the development of the fetus, in the onset and progression of most tumors and is found expressed in a few terminally differentiated cells. Altogether, there are ten splice variants of survivin, some of which are not yet satisfactorily characterized. Several isoforms may undergo homo/heterodimerization, particularly with the wild-type survivin to elicit a variety of biological functions. The detection of survivin and its splice variants not only suggests the onset, maintenance, and progression of cancer, but also the stage of certain cancers. Recent studies demonstrate that the presence of survivin in urine and blood samples of patients may suggest urogenital and bladder cancer hematologic malignancies, respectively. The expression of the survivin-3α splice variant is indicative of the onset and progression of breast cancer. Several companies have developed cancer diagnostic kits using survivin for detection of cancer. Some are also engaged in fine-tuning the type and stage-specific diagnosis of cancer based on survivin, its splice variants with and without other markers, such as hyaluronidase. Briefly, survivin and its splice variants hold a great biological significance, particularly in the diagnosis of cancer.

Urine survivin, E-cadherin and matrix metalloproteinases as novel biomarkers in children with chronic kidney disease.

CONTEXT: Epithelial-mesenchymal transition (EMT) leads to renal fibrosis and chronic kidney disease (CKD). OBJECTIVE: The aim of this study was to assess the usefulness of survivin, E-cadherin and metalloproteinases (MMPs) as biomarkers of CKD-related complications. MATERIAL AND METHODS: Survivin, E-cadherin, MMP-2, MMP-9 and TGFbeta1 were assessed by ELISA in 41 children with CKD stages 3 to 5 and in 23 controls. RESULTS: The serum and urine values of analyzed parameters were significantly elevated in CKD patients versus controls and correlated with each other. CONCLUSIONS: The observed parameter changes indicate apoptosis, tissue remodeling and fibrosis in CKD children. Urine survivin may become a new biomarker of kidney-specific EMT.

Detection of circulating tumor cells in bladder cancer using multiplex PCR assays.

AIM: The aim of this study was to develop multiplex-PCR assays for the detection of circulating tumor cells in peripheral blood and urine samples of patients with bladder cancer. MATERIALS AND METHODS: Peripheral blood and urine samples were collected from 208 patients (169 patients and 39 healthy volunteers). After RNA extraction and cDNA synthesis, the samples were analyzed for the expression of cytokeratin 19 (CK19), CK20 and epidermal growth factor receptor (EGFR) mRNA in blood and for SURVIVIN, human telomerase reverse transcriptase (hTERT), cytokeratin 20 (CK20) mRNA in urine, using multiplex-PCR assays. RESULTS: EGFR and CK20 alone or in combination as well as all urine markers correlated well with histological grade. hTERT correlated well with primary tumor size T≥3. Patients with positive urine markers had significantly worse progression-free survival. CONCLUSION: Multiplex-PCR assays can be a useful tool for staging and monitoring purposes in patients with bladder cancer.

Value of urinary survivin as a diagnostic marker in bladder cancer.

OBJECTIVE: To study the value of urinary survivin as a diagnostic marker for diagnosis of bladder cancer as compared to urine cytology. STUDY DESIGN: This study was carried out on 40 patients presenting with bladder cancer and 20 patients presenting with benign urological disorders. RESULTS: For bladder cancer diagnosis, urine cytology has lower sensitivity, accuracy, and negative predictive values as compared to survivin, while it has higher specificity and positive predictive value than survivin. On the other hand, the sensitivity, specificity, and the accuracy of combined survivin and urine cytology were 100%, 95% and 97%, respectively. Positive urine cytology and survivin were significantly higher in cases showing advanced stage and high grade as compared to cases presented with superficial stage and low grade. CONCLUSION: Urinary survivin appears to be a reliable, noninvasive diagnostic test to identify patients with bladder cancer. The sensitivity of survivin test was superior to that of urine cytology in the diagnosis of bladder cancer, especially in cases presenting with superficial stage or low grade. Combined evaluation of both survivin and urine cytology gave better sensitivity, specificity, and accuracy for bladder cancer diagnosis.

The diagnostic efficacy of urinary survivin and hyaluronidase mRNA as urine markers in patients with bladder cancer.

BACKGROUND: A new, sensitive, noninvasive method for the detection of urothelial carcinomas of the bladder would open new possibilities in both the diagnosis and follow up of patients. METHODS: Voided urine specimens were collected from patients with histologically confirmed bladder urothelial carcinoma (Group 1: n = 60), urological patients without urothelial carcinoma (Group 2: n = 20), and healthy volunteers (Group 3: n = 20). All underwent serological assessment of schistosomiasis antibody, quantitative measurement of survivin by ELISA in urine supernatant, urine cytology, and detection of hyaluronidase (HYAL-1) by RT-PCR in urothelial cells of voided urine samples. RESULTS: Urinary survivin mean rank was higher in malignant and benign groups than in the healthy group (p < 0.001). Urinary survivin best-cutoff was determined using receiver operating characteristic curve to discriminate between malignant and nonmalignant groups (2537.25 pg/mg protein) at 78.33% sensitivity and 82.5% specificity. HAase mRNA showed superior sensitivity (86.67%) over cytology (38.33%) and urinary survivin (78.33%) with specificity of 97.5%, 100%, and 82.5%, respectively. The sensitivity of urine cytology was increased on combination with either survivin (83.33%) or HAase (90%). Also, the combination of both markers increased overall sensitivity (95%). CONCLUSIONS: Survivin can be reliably and quantitatively measured in urine of bladder cancer patients, improving the sensitivity and specificity of urine cytology for the diagnosis of bladder cancer. Combined use of cytology with survivin and HAase was the best recommended combination for bladder cancer detection.

Diagnostic role of survivin in urinary bladder cancer.

BACKGROUND: Early diagnosis of carcinoma of bladder remains a challenge. Survivin, a member of the inhibitor of apoptosis (IAP) protein family, is frequently activated in bladder carcinoma. The objective of this study was to investigate urinary survivin as a marker for diagnosis of urinary bladder. MATERIALS AND METHODS: We examined urinary survivin concentration in 28 healthy individuals, 46 positive controls and 117 cases of histologically proven TCC prior to transurethral resection, using ELISA, and compared values with findings for urinary cytology. RESULTS: Survivin was found to be significantly higher in the cancer group (P<0.05). A cut off value of 17.7 pg/ml was proposed, with an approximate sensitivity of 82.9% and specificity of 81.1% (P<0.0001), whereas urine cytology had a sensitivity of 66.7% and a specificity of 96.0%. CONCLUSIONS: Urinary survivin can be used as a non-invasive diagnostic biomarker for TCC bladder, both for primary and recurrent disease.

The value of combined use of survivin mRNA and matrix metalloproteinase 2 and 9 for bladder cancer detection in voided urine.

OBJECTIVE: In a trial to improve the diagnostic efficacy of conventional urine cytology we determine survivin RNA and matrix metalloproteinase 2 and 9 in urine of bladder cancer cases. METHOD: Voided urine specimens were collected from patients with histologically confirmed bladder urothelial carcinoma (Group 1; n=46), urological patients without urothelial carcinoma (Group 2; n=20), and healthy volunteers (Group 3; n=20). Urine cytology, survivin RNA was estimated by qualitative nested RT-PCR and MMP-2, MMP-9 activity were detected by gelatin zymography. The expression of survivin RNA and matrix metalloproteinase 2 and 9 in bladder cancer was compared with benign and normal cases. RESULTS: Positivity rates of survivin RNA and MMPs zymography were significantly different among the 3 groups. Urine survivin detection by qualitative nested RT-PCR showed 76.1% sensitivity and 95% specificity. The overall sensitivity, specificity of urinary MMP zymography was 67.3%, 90% respectively. The combined use of urine cytology with urine survivin or MMPs zymography increased sensitivity of urine cytology from 50% to 84.7%. The highest sensitivity (95.6%) was obtained on combining the three markers. CONCLUSION: Survivin RNA and MMPS zymography can be considered as promising noninvasive markers for bladder cancer early detection. Combined use of the three markers improved the sensitivity for detecting bladder cancer.

THE SIGNIFICANCE OF EPIDERMAL GROWTH FACTOR RECEPTOR AND SURVIVIN EXPRESSION IN BLADDER CANCER TISSUE AND URINE CYTOLOGY OF PATIENTS WITH TRANSITIONAL CELL CARCINOMA OF THE URINARY BLADDER.

OBJECTIVE: To assess whether epidermal growth factor receptor (EGFR) and survivin immunostaining of tumour cells in urinary cytology and tissue of patients with bladder cancer has a prognostic significance. DESIGN: Prospective study SETTING: Department of Surgery (Division of Urology), Mubarak Al-Kabeer Teaching Hospital and Faculty of Medicine, Kuwait University, Kuwait SUBJECTS: Urine cytology smears obtainedpriorto cystoscopy in patients with transitional cell carcinoma (TCC) of the bladder were immunostained for EGFR and survivin. Bladder cancer tissue resected at surgery was also immunostained for EGFR and survivin expression. Tissue expression of EGFR and survivin in TCC of the bladder was compared to their expression in urine cytology and relationship to tumour grade and stage. RESULTS: 178 patients were studied (43 newly diagnosed bladder cancer, 58 with recurrent TCC and 77 in disease remission). Twenty five patients with normal urothelium served as controls. The mean sensitivity of urine cytology, tissue survivin immunohistochemistry (IHC) and tissue EGFR IHC was 30.5%, 62% and 59% respectively. The corresponding mean specificity was 95%, 79% and 38% respectively. For grades 1, 2 and 3 bladder tumors, tissue expression positivity for EGFR was 47.8%, 92.9%, 100% and for tissue survivin it was 27.8%, 18.2% and 33.3% respectively. For grades 1, 2 and 3 bladder tumors, urine expression positivity for EGFR was 35.7%, 40% and 67.7% and for urine survivin it was 8.3%, 42.9% and 33.3% respectively. CONCLUSION: Positive EGFR immunostaining of urine cytology specimen or tumour tissue increases with histological grade of TCC of the bladder. Survivin expression is less consistent in both urine cytology specimen and tissue samples. EGFR immunostaining may provide a useful tool in the grading of bladder TCC and aid in the selection of patients that may benefit from administration of EGFR inhibitors.

[Value of combined detection of urinary Livin and Survivin mRNA expression in the early diagnosis of bladder cancer].

OBJECTIVE: To evaluate the value of urine Livin and Survivin mRNA expression in the early diagnosis of bladder cancer. METHODS: Fifty-two cases of early bladder cancer and 30 cases of non-urinary system tumors were selected for the combined detection of urinary Livin and Survivin and urine cytology. RESULTS: Livin and Survivin in urine and urinary cytology sensitivity were 71.2% (37/52) , 67.3% (35/52), 23.1% (12/52); Specificity were 96.7% (29/30) , 93.3% (28/30) and 96.7% (29/30) respectively. Urine Survivin sensitivity, specificity compared with Livin were no significant difference (all P > 0.05). Urinary Livin and Survivin were more sensitive than urine cytology, and the differences were statistically significant(all P < 0.05). CONCLUSION: The combined urinary detection of Livin, Survivin mRNA expression is a noninvasive early diagnosis of bladder cancer with sensitivity and specificity.

Urine survivin as a diagnostic biomarker for bladder cancer: a systematic review.

What's known on the subject? and What does the study add? Although many tests for identifying patients with new or recurrent bladder cancer have been used, a reliable method has yet to be established. Recently, increasing attention has focused on the role of survivin in bladder cancer detection. Because urine survivin tests have better sensitivity than cytology, urine survivin could potentially replace routine cytology and might be used as an adjunct method for cystoscopy. However, the clinical utility of urine survivin as a bladder tumour marker identified in the present study remains to be elucidated. To determine the clinical utility of urine survivin as a bladder tumour marker we systematically reviewed the available evidence. A comprehensive literature review was performed, from August 1997 to March 2011, using three search engines in English including PubMed, Cochrane Library, and SCOPUS. Two reviewers independently evaluated both trial eligibility and methodological quality and data extraction. We included studies that evaluated urine survivin, used cystoscopy and/or histopathology as the reference standard, and allowed the construction of a 2 × 2 contingency table. Bivariate random effect meta-analyses were used to calculate the summary estimated of sensitivity and specificity and to construct a summary receiver-operating characteristics curve of urine survivin tests. In all, 14 studies were included in the present review; two studies had two subsets of data. There were 2051 subjects, including 1038 in the case group and 1013 in the control group, and heterogeneity was present among diagnostic studies. The pooled sensitivity and specificity for urine survivin tests were 0.772 (95% confidence interval [CI] 0.745-0.797) and 0.918 (95% CI 0.899-0.934), respectively. The area under the curve of urine survivin tests was 0.9392. When a subgroup analysis with six studies was performed, urine survivin tests had better sensitivity than cytology, but did not match cytology for specificity. The clinical utility of urine survivin as a bladder tumour marker identified in the present study remains to be elucidated.

Predictive values of urinary bladder tumor markers survivin and soluble-Fas comparison with cystoscopy and bladder tumor antigen.

AIM: The aim of the study was to evaluate the predictive values of two novel urinary markers for bladder cancer: survivin and soluble-Fas (s-Fas). METHODS: The study included 84 individuals divided in two groups. The first group contained 47 patients, who underwent transurethral bladder tumor resection and the second, control, group 20 patients with non-malignant conditions, who underwent cystoscopy and 17 health volunteers. Fresh, second morning voided urine was collected for measurement of s-Fas, survivin, BTA and for cytology. Sensitivity, specificity, positive and negative predictive values and accuracy were calculated. RESULTS: Bladder tumor patients had significantly higher survivin urine levels in comparison to the controls. Survivin correlated also with the tumor stage. Combination of survivin with BTA had a sensitivity of 86.4% but still lower than that of cystoscopy (97.8%). Only the specificity of the combination between survivin and BTA was higher than that of cystoscopy (86.4% and 75.6%, respectively). CONCLUSION: Survivin was a better marker for tumor detection than s-Fas and was better enough to discriminate cancer stage. Combination of survivin and BTA had a specificity of 86.4% to exclude bladder malignancy and the combination of s-Fas with survivin and BTA had a sensitivity of 93.6% to detect bladder cancer.

Detection of nuclear matrix protein 22 and survivin baseline level in patients after radical cystectomy.

We investigated the baseline levels of urine nuclear matrix protein 22 (U-NMP22) and survivin in urine after radical cystectomy for primary invasive bladder cancer. We measured U-NMP22 and survivin values in 72 patients with four types of urinary diversion (Indiana bladder, Bricker bladder, Mainz bladder and orthotopic bladder) after radical cystectomy and 25 healthy volunteers. We also analyzed the relation between the U-NMP22 and survivin level and other variables among patients with continent urinary diversion and incontinent urinary diversion as well as healthy controls, and found that the U-NMP22 and survivin values were not associated with postoperative interval or gender. The U-NMP22 values (mean ± standard error) for continent urinary diversion, incontinent urinary diversion and healthy controls were 12.08 ± 0.10, 16.62 ± 0.15 and 0.01 ± 0.00 U/ml, respectively. The survivin values (mean ± standard error) for continent urinary diversion, incontinent urinary diversion and healthy controls were 0.47 ± 0.06, 0.69 ± 0.16 and 0.02 ± 0.03 U/ml, respectively. The U-NMP22 and survivin values in the Bricker bladder group were significantly higher than the values in the other three groups. We noted that increased levels of U-NMP22 and survivin after radical cystectomy varied according to different predictors, which may be useful for designing strategies to follow these cases.

[Usefulness of survivin/glyceraldehyde-3-phosphate dehydrogenase ratio in urine exfoliated cells for the detection of bladder tumor].

OBJECTIVE: Survivin is one of the apoptosis inhibitor proteins and is rarely expressed in adult normal tissues. However, survivin expression has been detected in various tumors. In this study, we evaluated the usefulness of urinary survivin/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) ratio as a marker for bladder tumor. PATIENTS AND METHODS: Urine samples were obtained from 72 patients with bladder tumor, 36 with urinary tract inflammation as controls. Survivin and GAPDH mRNA expression was measured by quantitative real-time PCR assay in urine cells. The GAPDH housekeeping gene was used for normalization of survivin expression. We also analyzed survivin protein levels using urine samples and recombinant protein by western blotting. RESULTS: High expression of survivin was confirmed on the protein level using urine samples of bladder tumor by western blotting. Survivin/GAPDH mRNA ratios of bladder tumor quantified by real-time PCR was significantly higher than those of controls (p=0.001). In pathological stage of bladder tumor, survivin/ GAPDH mRNA ratio of pTis was significantly high compared with pTa and pT1 (p < 0.001, p=0.001, respectively). Grade3 tumors expressed high level of survivin/GAPDH mRNA ratio compared with Grade 1 and Grade 2 tumors (p=0.03). The sensitivity, the specificity and AUC(area under the curve) of survivin/ GAPDH mRNA ratio was 83.3%, 86.1% and 0.898, respectively. CONCLUSION: Measuring survivin/GAPDH mRNA ratio in urine is non-invasive and high sensitive examination. Therefore, survivin/GAPDH mRNA ratio is useful marker for the detection of bladder tumor, especially to detect carcinoma in situ.

[Bladder cancer screening with urine-based tumour markers - occupational medical experience]. / Das Screening von Harnblasenkarzinomen mittels urinbasierter Tumormarker - Erfahrungen aus der Arbeitsmedizin.

OBJECTIVE: Bladder cancer responds favourably to treatment and has a good survival rate, provided it is diagnosed at an early stage. Established methods exist for the early detection, however, their specificity and positive predictive value are not yet satisfactory. Innovative markers have been proposed, but still require validation in prospective studies. We provide a literature-based short overview on the currently available and some proposed markers for the early detection of bladder cancer and evaluate the need for validation in further studies. We further provide some first results of such a recently finished study in an occupational setting. MATERIAL AND METHODS: We conducted a prospective screening study over seven years in 1610 males with former occupational exposure to carcinogenic aromatic amines. Annual bladder cancer screening according to statutory requirements was offered. In addition to the regularly performed check for hematuria and urine cytology, the markers NMP22, UroVysion™ and survivin were performed in voided urine samples of the participants. Positive findings (not for survivin) were further followed through urethrocystoscopy. RESULTS AND CONCLUSIONS: A total of 7219 urine samples were screened. During the study period 16 incidental and 4 recurrent bladder tumours, thereof three papillomas, occurred in a total of 19 participants. 14 out of twenty tumours were marker-positive, and all but two were early stage findings. Cell-based markers (cytology, UroVysion™) und molecular markers (NMP22, survivin) were largely complementary, thus acting as a "multi-marker panel". Eight of the tumours were identified by a positive cytology. Six tumours were not detected by any of the tumour markers. The results will be further evaluated through the inclusion of confounding factors, which have so far rarely been examined in other studies. This may lead to the development of tiered diagnostic strategies with the aim to reduce the number of invasive diagnostic procedures in the future.

The diagnostic value of urine-based survivin mRNA test using reverse transcription-polymerase chain reaction for bladder cancer: a systematic review.

BACKGROUND AND OBJECTIVE: Survivin has gradually become an important target in diagnosis, prognosis prediction and treatment of tumor. There are many studies on urine-based survivin mRNA test using reverse transcription-polymerase chain reaction (RT-PCR) as a noninvasive examination for bladder cancer. However, its clinical value remains controversial. This study was to evaluate the diagnostic value of urine survivin mRNA detection with RT-PCR for bladder cancer by a systematic review of related studies. METHODS: With the search terms such as bladder neoplasm, survivin, RT-PCR, sensitivity, specificity and diagnosis, we systematically searched through PubMed, EMBASE, SCI, Cochrane Library, Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Full-text Database (CSJD), China Journal Full-text Database (CJFD), Chinese Medical Association (CMA) digital periodicals and Google Scholar totally from January 1997 to April 2009 for diagnostic trials with RT-PCR detection of urine survivin mRNA for bladder cancer. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) items were used to evaluate the quality of the included studies. Meta-disc software was used to calculate outcome indicators. RESULTS: Twenty-six studies, totally 2 416 patients, were eligible. Meta-analysis showed that compared with pathologic examination, the summary values of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and summary receiver operating characteristic curve (SROC) of urine-based survivin mRNA test using RT-PCR for bladder cancer were 88%, 94%, 14.56, 0.13 and 0.9736, respectively. Nested RT-PCR got the highest sensitivity, specificity and SROC and the values were 91%, 95% and 0.9805, respectively. The sensitivity and specificity of general RT-PCR were the second highest, which were 87% and 94%, respectively. The sensitivity of quantitative RT-PCR was 80% and the specificity was 93%. CONCLUSIONS: Comparing with pathologic examination, the sensitivity and specificity of urine-based survivin mRNA test using RT-PCR are relatively high. It can be used as an important adjunct method for cystoscope in early screening and postoperative monitoring of bladder cancer.

[Expression of survivin mRNA in urine exfoliated cells of patients with bladder transitional cell carcinoma detected by real-time PCR].

BACKGROUND AND OBJECTIVE: Bladder cancer is the most malignant cancer of the urinary system. However a noninvasive and sensitive method of the early diagnosis for bladder cancer has not been developed. This study was to explore the expression of survivin mRNA in urine exfoliated cells of preoperative and postoperative patients with bladder transitional cell carcinoma (BTCC), and to analyze its value in early diagnosis and postoperative monitoring. METHODS: Urine of 30 patients with initially diagnosed BTCC was collected before operation and one week, one month, six months and 15 months after operation. Urine of 10 healthy volunteers and 15 patients with cystitis was used as control. Expression of survivin mRNA in urine exfoliated cells was detected by real-time fluorescent quantitative polymerase chain reaction (real-time PCR). RESULTS: The relative copy number of survivin mRNA in the patients was (96.01+/-42.33) before operation, which was significantly higher than that of healthy volunteers and cystitis patients (P <0.05). The level of survivin mRNA was apparently declined one week after operation (25.30+/-1.51) compared with its preoperative level (P <0.05); and the level became as low as the control group after one month (13.20+/-1.49) and six months (13.90+/-1.36) (P>0.05). Patients were followed up for 15 months, and three patients recurred, whose survivin mRNA level (97.83+/-27.47) was significantly higher than that at six months after operation (P <0.05). CONCLUSION: Detecting survivin mRNA in urine exfoliated cells is sensitive for the diagnosis of BTCC. Detection survivin mRNA after operation can monitor recurrence.

[Clinical evaluation of BTAstat, NMP22, HA, survivin, CD44v6, vEGF and VUC in bladder cancer diagnosis].

OBJECTIVE: To evaluate the sensitivity and specificity of BTAstat, NMP22, HA, Survivin, CD44v6, VEGF, and VUC in detection of bladder cancer. METHODS: We detect VUC, BTAstat, NMP22, HA, Survivin, CD44v6, VEGF in the urine of 10 normal case (healthy volunteers), 11 benign urological diseases patients and 52 bladder cancer patients. The sensitivity, specificity the coefficient of variation, the examining time duration and the checking costs of each marker and combined markers were assessed to evaluate the clinical value. RESULTS: There is a significant difference between the cancer group and the two control groups. The overall sensitivity and specificity of urinary tumor markers were: 42.3% and 100% for VUC; 78.8% and 90.5% for BTAstat; 76.9% and 81.0% for NMP22; 86.5% and 90.5% for HA; 67.3% and 85.7% for Survivin; 50.5% and 85.7% for CD44 and 69.2% and 95.2% for VEGF. The highest sensitivity of combined markers was 96.2% for NMP22 + HA and HA + CD44v6, whereas the lowest sensitivity of combined markers was 67.3% for VUC + CD44v6. The highest specificity (95.2%) was the combined use of VUC + NMP22 and combined use of VUC + VEGF, whereas, method that achieved the lowest specificity (66.7%) was the combined use of HA + Survivin. The most convenient examining method was the detection for BTAstat; the lowest cost examining method was the detection for HA; methods which had the best repeatability were the detection for BTAstat and urine cytology examination. CONCLUSION: Each marker had achieved its obvious clinical value in diagnosis of bladder cancer. The sensitivity of all the markers was increased with the progression of tumor grades and clinical stages, except the CD44v6. The combined use of BATstat and HA is the best examining method concerning sensitivity, specificity, feasibility and cost in each different method.