Muscle-Invasive Transitional Cell Carcinoma of the Urinary Bladder is Associated with Down-Regulated CPP32 Expression and BCL-2 Positivity

• Published in: Journal of medical biochemistry Vol. 28; no. 2; pp. 101 - 107
• Main Authors: Pljesa-Ercegovac, Marija, Mimic-Oka, Jasmina, Dragicevic, Dejan, Savic-Radojevic, Ana, Matic, Marija, Dukic, Tatjana, Simic, Tatjana
• Format: Journal Article
• Language: English
• Published: Belgrade Versita 01.04.2009; Society of Medical Biochemists of Serbia; Society of Medical Biochemists of Serbia, Belgrade
• Subjects: apoptosis; apoptoza; Bcl-2; CPP32; invazivni karcinom prelaznog epitela; mokraćna bešika; TCC; urinary bladder
• ISSN: 1452-8258; 1452-8266
• DOI: 10.2478/v10011-009-0009-8

The objective was to get insight into the role of executive apoptotic enzyme caspase 3 (CPP32) and regulatory antiapoptotic protein Bcl-2 in the malignant phenotype of TCC. Samples were obtained from 84 TCC patients, who underwent transurethral resection, partial or radical cystectomy. Staging showed a superficial growth pattern in 41 patient, while other 43 showed invasive characteristics. Expression of CPP32 and Bcl-2 was determined by immunocytochemistry. Levels of expression were correlated with tumor stage and grade. Expression of CPP32 was positive in 80% of TCC patients. Low-, medium- and high positive status were observed in 18%, 24% and 38% of patients, respectively. There was a signifficant difference in the CPP32 expression between groups with superficial and invasive TCC tumors (p = 0.032), with frequency of CPP32 negative samples being higher and CPP32 high-positive samples being lower in patients with muscle-invasive tumors. Significant association was also found between CPP32 expression and tumor stage (p = 0.043). The positive rate of Bcl-2 protein expression was 48%. There was a statisticaly signifficant difference in the rate of Bcl-2 positivity between superficial and invasive TCC (p = 0.005), with frequency of Bcl-2 positive patients being higher in muscle-invasive TCC. Significant association was also found between Bcl-2 expression and both tumor grade (p=0.032) and stage (p=0.007). Muscle invasive TCC of the urinary bladder is associated with down-regulated expression of CPP32 and Bcl-2 positivity. Down-regulation of CPP32 and up-regulated Bcl-2 might, at least partially, play a role in the development of invasive characteristics of TCC. Ispitivana je uloga izvršnog molekula apoptoze, kaspaze 3 (CPP32) i regulatornog antiapoptotskog proteina Bcl-2 u malignom fenotipu karcinoma prelaznog epitela mokraćne bešike. U istraživanju su korišćeni uzorci tumorskog tkiva mokraćne bešike 84 bolesnika sa karcinomom prelaznog epitela, koji su podvrgnuti transuretralnoj resekciji, parcijalnoj ili radikalnoj cistektomiji. Na osnovu stepena invazivnosti, uzorci su podeljeni u dve grupe: 41 neinvazivni tumor i 43 invazivna tumora. Ekspresija CPP32 i Bcl-2 određivana je metodom imunocitohemije. Ispitivana je povezanost nivoa ekspresije sa stepenom maligniteta i stadijumom tumorske bolesti. Ekspresija CPP32 bila je pozitivna u 80% uzoraka tumorskog tkiva pacijenata sa karcinomom prelaznog epitela. Slabo pozitivno bojenje je uočeno u 18%, umereno pozitivno u 24%, a veoma pozitivno u 38% pacijenata. Uočena je statistički značajna razlika u ekspresiji CPP32 između neinvazivnih i invazivnih karcinoma (p=0,032), pri čemu je učestalost CPP32 negativnih pacijenata bila veća, a CPP32 veoma pozitivnih pacijenata manja u invazivnim karcinomima. Značajna povezanost je uočena i između smanjene ekspresije CPP32 i stadijumima tumora (p=0,043). Prisustvo antiapoptotskog Bcl-2 proteina je utvrđeno u 48% uzorakak tumorskog tkiva. Statistički značajna razlika u učestalosti Bcl-2 pozitivnih pacijenata je uočena između neinvazivnih i invazivnih tumora (p=0,005), pri čemu je učestalost Bcl-2 pozitivnih pacijenata bila veća u grupi invazivnih karcinoma. Statistički značajna razlika je uočena između ekspresije Bcl-2 i stepena maligniteta (p=0,032), kao i stadijuma tumorske bolesti (p=0,007).