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Expression Of Survivin And HTERT Protein In Bladder Transitional Cell Carcinoma And Their Clinical Significance

Posted on:2005-12-22Degree:MasterType:Thesis
Country:ChinaCandidate:Z J GuoFull Text:PDF
GTID:2144360125952453Subject:Urology
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Bladder transitional cell carcinoma ( BTCC ) possessing complicated biological behavior, is the most common malignancy in the genitourinary tract in China. In order to improve the overall survival rate of bladder cancer patients, large and increasing interest has been focused on searching markers with diagnostic and/or prognostic value.Recent years, lots of studies have been done on the role of survivin and hTERT in neoplasm including BTCC. Survivin is a member of the inhibitor-of-apoptosis proteins ( IAPs ) family, commonly detected in tissues during fetal development and in cancers, but not usually in adult normal tissues. Survivin protein has the ability to suppress apoptosis (programmed cell death) and regulate cell division. hTERT is one of the three essential components of telomerase and considered to be the key enzyme to active telomerase, its expression is limited to cells that show telomerase activity. Telomerase is an enzyme that can reconstitute the ends of chromosomes after cell division and thus circumvent the damage that occurs in normal adult somatic cells during successive mitotic cycles, its activation represents an important step in cell immortalization and carcinogenesis. Survivin and hTERT both play pivotal role in the initiation and development of neoplasm through different mechanisms. Expression of survivin protein and/or hTERT protein may be of diagnostic and/or prognostic significance in many cancers.In the current study, the expression of survivin and hTERT wereexamined in 56 cases of bladder transitional cell carcinoma, 8 normal bladder mucosas, 10 inverted papilloma and 6 atypia hyperplasia by means of immunohistochemistry(IHC). Immunostain was recorded as 0~2+ according to stain intensity, distribution in cytoplasm and / or nucleus. The correlations between the expression results and tumor pathological grades, clinical stages, number of lesions, recurrence were also studied.Survivin and hTERT expression were observed mainly in cytoplasm. Survivin and hTERT expression were found in 41/56 and 50/56 cases of bladder cancer tissues (73.2%, 89.3% sensitivity) , in 4/24 and 5/24 cases of non-cancerous bladder tissues (83.3%, 79.2% specificity), the sensitivity of hTERT was significantly better than that of survivin. The positive expression rates of survivin in grade G1-G2 G3 were 56.3% 95.8 %, in stage of Ta-T1 T2-T4 were 61.8% 90.9% , in primary recurrence cases were 65.8%^ 88.9%, and in multiple solitary tumors were 85.7% 65.7%, respectively. The expression of survivin was significantly positively related to grade, stage and recurrence (P<0.05) .Furthermore, its stain intensity increased with the advance of tumor grade and stage. The positive expression rate of hTERT in BTCC (89.3%) was significantly higher than that in non-cancerous bladder tissues (20.8%) ,but no prognostic value has been observed. The positive expression rates of hTERT in grade G1-G2 (87.5%) and in stage of Ta-Tl (85.3%) were significantly higher than that of survivin( 56.3%,61.8%), respectively.These results suggest that abnormal hTERT expression may be acritical molecular step in the initiation of TCC, and survivin may play an important role in the initiation and progression of TCC through inhibiting cell apoptosis. Both hTERT and survivin are promising tumor markers for early detecting BTCC, hTERT examination has much higher sensitivity in diagnosing BTCC. Detection of survivin expression might be helpful in predicting the biological behavior of bladder transitional cell carcinoma.
Keywords/Search Tags:Bladder neoplasms, Immunohistochemistry (IHC), Survivin, Telomerase, Transitional cell carcinoma ( TCC ), Human telomerase reverse transcriptase ( hTERT )
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