Letters 2119 4. Sperti C, Pasquali C, Catalini S, et al. CA19-9 as a prognostic index after resection for pancreatic cancer.9 Surg On& 1993,52,137-141. 5. Wong A, Chan A. Survival benefit of tamoxifen therapy in adenocar- cinema of pancreas. A case-control study. Cancer 1993, 71, 2200-2203. Acknowledgements-Supported by a research grant from Alberta Cancer Board, Research Initiative Clinical Trials Program, Project No. CT-6. The authors wish to thank Dr Michael Weaver and Mrs Doris Schuh of the Immunochemistry Laboratory, Foothills Hospital for their assistance in this study. Europcon~oumafofCan~Vol. 31A,No. 12,~p.211!%2120,1995. Blswier Science Ltd Printed in Great Britain 0959-m9/95 $9.50 + 0.00 0959-8049(95)oo404-1 Detection of BCL-2 RNA in Low Grade Tumours of the Urinary Bladder P. Gazzaniga,’ M. Gallucci,2 A. Gradilone,’ 0. Gandini,l A. Vincenzoni,2 W. Gianni,3 G. Naso,’ L. Frati’ and A.M. Agliano’ ‘Dipartimento di Medicina Sperimentale e Patologia, Universith degli Studi di Roma “La Sapienza”; 2Divisione di Urologia, Ospedale Cristo Re; and 31Clinica Medica, Universid degli Studi di Roma “La Sapienza”, Rome, Italy zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA THE MAINTENANCE of homeostasis in normal tissues can be considered a balance between cell proliferation and cell death; thus any condition that alters these parameters may contribute to tumour development. While most oncogenes are believed to influence the cellular proliferation rate or differentiation, BCL-2 overexpression suppresses the active cell death process referred to as apoptosis [l]. BCL-2 proto-oncogene, originally described at the breakpoint site of the chromosomal translocation t( 14;18) in a follicular lymphoma [2], is now known to be involved in a variety of haemopoietic [3] and solid tumours [4, 51, where its presence is often associated with chemotherapy resistance [6]. Despite its association with some forms of human cancer, a number of normal tissues examined by immunohistochemistry have been shown to lack BCL-2; these include lung, liver, heart, cervix, ovary, testis, kidney and bladder [7]. Bladder cancer is the lifth common cancer in men in the Western society, being responsible for 5% of all cancer deaths. The 5 year survival rate is highly dependent on the pathological Correspondence to Anna Maria Aglianb, Dipartimento Medicina Speri- mentale e Patologia, Viale Regina Elena, 324,00161 Rome, Italy. Revised 30 May 1995; accepted 14 Jul. 1995. 123456789 (a) 304 bp (b) 123456789 304 bp Figure 1. Autoradiography of RT-PCR products blotted and hybrid- ised with a 32Poligonucleotide probe specific for BCL-2. (a) Lane 1: negative contml for BCL-2 expression (HeLa cell line); lanes 2-g: urinary bladder tumour tissue; lane 9: positive control for BCL-2 expression (CaSld cell line). (b) Lanes 1 and 9: the same as in (a); lanes 2-g: adjacent normal tissues corresponding to samples 2-g shown ia (a). stage, and ranges from 10% for patients with pT4 tumours to 70% for those with pT2. In recent years, molecular studies have concentrated on the identification of ‘initiating’ factors and markers for disease progression, with a view to early diagnosis and follow-up of patients with low grade disease [8]. In order to better investigate the role of BCL-2 in the very early stage of the disease, we analysed by RT-PCR (Reverse Transcriptase-Polymerase Chain Reaction) 30 low grade tumours from the urinary bladder (Ta, Tis, Tl and T2) and normal adjacent bladder tissue. While we found the expression of BCL-2 at the RNA level in 19/30 (63%) of the tumour samples, no expression was detected in any normal tissue (Figure 1). To our knowledge, this is the first report of BCL-2 expression in urinary bladder turnours. BCL-2 is known to block programmed cell death, giving the cells that overexpress the protein a survival advantage over normal cells. Thus, the expression of BCL-2 in low grade bladder tumours and its absence in adjacent normal tissue may suggest its possible implication in the initiation of the multistep process of bladder carcinogenesis. Alternatively, the finding that not all the low grade lesions examined expressed BCL-2 at the RNA level suggests a possible role of this gene in the more rapid evolution, observed in some types of bladder cancer, toward metastatic growth and invasion. In conclusion, BCL-2-expressing tumours may have different clinical behaviour in comparison with those that do not, as previously described for prostate tumours and other neoplasms, where the overexpression of this gene has been often correlated to chemotherapy resistance, poor prognosis, and decreased survival of the patients. This would be of some importance in the screening of low grade bladder cancer and in the follow-up of the post-TUR (transurethral resection) patients. 1. 2. 3. 4. 5. Osborne BA, Schwartz LM. Essential genes that regulate apoptosis. Trend? Cell Bioll994,4,394-398. Tsujimoto Y, Cossman J, Jaffe E, Croce C. Involvment of the bcl-2 gene,in human follicular lymphoma. Science 1985,228,1440-1443. Aisenberg AC, Wilkes BM, Jacobson JO. The bcl-2 gene zyxwvutsrqponmlk is rearranged in many diffuse B-cell lymphomas. Blood 19&X8,71,%9-972. Hague A, Moorghen M, Hicks D, et al. Bcl-2 expression in human colorectal adenomas and carcinomas. Oncogene 1994,9,3367-3370. Joensuu H, Pylkkanen L, Toikkanen S. Bcl-2 protein expression and long term survival in breast cancer. AmJ Path 1994,145,1191-l 198.