Expression of survivin and its spliced variants in bladder tumors as a potential prognostic marker.
BACKGROUND
Survivin, a novel inhibitor of apoptosis, is re-expressed in a vast majority of human cancers and is widely considered as a diagnostic marker of cancers. Survivin protein regulates both cell division and apoptosis. There are at least 5 spliced variants of the gene with different subcellular localization and anti-apoptotic property. We examined the expression pattern of survivin and its 2 spliced variants, survivin-deltaEx3 and survivin-2B, and their prognostic values in archival collections of formalin-fixed paraffin-embedded samples of bladder tumors.


METHODS
Total RNA from formalin-fixed paraffin-embedded samples (51 samples from 30 patients with bladder cancer and 5-year follow-up) were extracted and analyzed by semiquantitative reverse transcriptase polymerase chain reaction technique. Tissue distribution and subcellular localization of survivin protein in tumor tissues was also examined by immunohistochemistry.


RESULTS
The expression of survivin, survivin-deltaEx3, and survivin-2B were detected in 66.6%, 47.8%, and 54.7% of the specimens, respectively. The expression of survivin and survivin-deltaEx3 were preferentially elevated in tumors with higher grades, whereas survivin-2B expression was lower in high-grade tumors (P = .04). A reverse correlation was observed between survivin-2B expression and high-grade tumors. Immunohistochemistry results also confirmed the nuclear localization of survivin protein within tumoral cells.


CONCLUSIONS
We were successful in detecting the expression of survivin and its variants in formalin-fixed paraffin-embedded bladder samples. Furthermore, our results showed that overexpression of survivin and survivin-deltaEx3 in bladder tumors correlates with poor prognosis of bladder cancer. We suggest that survivin and its variants are suitable prognostic markers of bladder tumors.
Nouraee
Nazila
N
Department of Genetics, Faculty of Basic Sciences, Tarbiat Modarres University, Tehran, Iran.
Mowla
Seyed Javad
SJ
Ozhand
Ardalan
A
Parvin
Mahmoud
M
Ziaee
Seyed Amir Mohsen
SA
Hatefi
Nasim
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D015331:Cohort Studies; D015653:Cystectomy / Q000379:methods / Q000401:mortality; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012326:RNA Splicing; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D000077022:Survivin; D046509:Tissue Culture Techniques; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery
C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D000077022:Survivin