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Nuclear Matrix Protein 22, Cytokeratin 20 And Survivin As Diagnostic And Prognostic Markers For Bladder Tumor

Posted on:2005-11-08Degree:DoctorType:Dissertation
Country:ChinaCandidate:J H WanFull Text:PDF
GTID:1104360125965327Subject:Surgery
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Bladder carcinoma is the most common seen tumor in urinary tract.More than 90% of bladder carcinoma is transitional cell carcinoma(TCC).More than 80% of TCC of the bladder is superficial bladder carcinoma(SBC).Recurrence of TCC of the bladder is high.More than 50% to 90% of SBC recur within 5 years while 10% to 20% progress to invasive disease. Successful management depends on regular follow-up and early detection of persistent or recurrent carcinoma.The most accepted surveillance for patients is based on cystoscopy,the reference diagnostic method for bladder cancer detection,with additional information provided by urinary cytology(UC).Unfortunately,the sensitivity of UC is on average less than 50% and as low as 30%in low stage,low grade disease.In current protocols patients with bladder cancer undergo cystoscopy every 3 months for 1 year or 2 year,every 6 months for another 2 years.The potential development of highly sensitive and specific markers for the detection of TCC of the bladder could have an impact on improving effectively diagnosis and management,as well as reducing the number of cystoscopies.More than 90% of SBC is grade 1 or grade 2 tumors.Despite there being well difined criteria for the grading of SBC,many reports have shown 30% to 40% variability among pathologists.The development of objective markers to predict the recurrence of the SBC has important clinical significance in establishing treatment and follow-up protocal.NMP22,CK20 and Survivin are potential diagnostic markers for TCC of the bladder have been reported recently.Some reports appeared that the NMP22 test had high sensitivity,however,another reports did not appear to be.There is disputation in determine the expression of CK20 in cells separated from the urine of patients with bladder carcinoma.Only the preliminary study of urine detection of survivin in diagnosis of bladder cancer was reported.As we know,there is no report about comprehensive comparison dignostic values of urinary NMP22,CK20 and Survivin with UC in bladder cancer,as well as prediction value of tumor relapse of Survivin expression in tissues of the SBC.This perspective clinical study compared the diagnostic values of NMP22,CK20 and Survivin with UC by means of ELISA and RT-PCR methods and so on.We observed the expression of CK20 and Survivin patterns in SBC through immunocytochemical method and analysed the correlation between the expression patterns of CK20 or Survivin and tumor relapse.We also examined the clinical categories of the false-positive results,established relative exclusion criteria.in the end,we investigated the effect of the degree of RBC on NMP22 results in healthy individuals.The main results are as follows:1. The overall sensitivities and specificities for the NMP22,CK20,Survivin and UC were 81.9%,86.1%,83.3%,31.9% and 61.0%,63.4%,90.2%100%,respectively. NMP22, CK20,Survivin had significantly higher sensitivities than UC,but lower specificities than UC.2.Of 42 primary SBC patients,10 had tumors with a normal pattern of CK20 expression, no one developed further tumor during the follow-up (median 17 [range 10-28] months).By contrast,15 of the 32 patients (46.9%) with tumors that showed abnormal CK20 expression developed further tumors.12 of 24 patients (50%) whose tumors had positive Survivin expression experienced a recurrence during the follow-up.however,only 3 of 18 patients (16.7%) whose tumors had negative Survivin expression experienced a recurrence.3. The false-positive results included 6 clinical categories:benign inflammatory,urinary calculi,presence or history foreign body,bowel interposition segment, other genitourinary cancer,instrumentation.Exclusion of these categories improved the specificity and positive predictive value of NMP22 to 96.2% and 95.2%,respectively.4. When blood was added to the urine sample of a healthy individual,the NMP22 increase paralleled the increase in the amount of RBC.When greater than 2μL/mL blood were added to the urine, the NMP22 level reached the level in patients with bladder carcinoma.The...
Keywords/Search Tags:bladder carcinoma, nmp22, cytokeratin 20, survivin, recurrence
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