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. 1997 Feb;50(1):28–33. doi: 10.1136/mp.50.1.28

Expression of bcl-2 in bladder neoplasms is a cell lineage associated and p53-independent event.

Q L Lu 1, M Laniado 1, P D Abel 1, G W Stamp 1, E N Lalani 1
PMCID: PMC379576  PMID: 9208811

Abstract

AIMS: To investigate bcl-2 and p53 protein expression in hyperplastic, metaplastic and neoplastic epithelia of the urinary bladder in relation to cell lineages (transitional versus glandular epithelia). METHODS: Formalin fixed, paraffin wax embedded archival tissue blocks of 29 transitional cell carcinomas (TCC), 11 adenocarcinomas, five specimens of cystitis glandularis, four papillomas, and seven samples of morphologically normal bladder mucosa were examined immunohistochemically with antibodies specific to bcl-2 and p53. Consecutive sections were used to assess co-expression of the two proteins. RESULTS: bcl-2 protein was expressed heterogeneously in basal cells of the normal transitional epithelium, whereas p53 was rarely detectable in either normal or hyperplastic epithelium. Of the 29 TCCs, 20 (69%) expressed immunodetectable p53 which was positively associated with grade. In contrast, bcl-2 was detected in four (14%) TCCs and its expression was not associated with grade. bcl-2 was expressed constitutively in all five specimens of cystitis glandularis and in all adenocarcinomas; p53 was co-expressed in most of the latter. There was no association between bcl-2 and p53 protein expression in the TCCs. Expression of bcl-2 protein correlated negatively with grade of adenocarcinoma. CONCLUSION: In bladder adenocarcinomas, bcl-2 expression correlated negatively with tumour grade whereas p53 was associated positively with tumour grade. The association of bcl-2 with cystitis glandularis and adenocarcinoma but not TCC suggests that it may be involved in triggering a lineage switch converting transitional epithelium to a glandular phenotype.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bosari S., Moneghini L., Graziani D., Lee A. K., Murray J. J., Coggi G., Viale G. bcl-2 oncoprotein in colorectal hyperplastic polyps, adenomas, and adenocarcinomas. Hum Pathol. 1995 May;26(5):534–540. doi: 10.1016/0046-8177(95)90250-3. [DOI] [PubMed] [Google Scholar]
  2. Bronner M. P., Culin C., Reed J. C., Furth E. E. The bcl-2 proto-oncogene and the gastrointestinal epithelial tumor progression model. Am J Pathol. 1995 Jan;146(1):20–26. [PMC free article] [PubMed] [Google Scholar]
  3. Channer J. L., Williams J. L., Henry L. Villous adenoma of the bladder. J Clin Pathol. 1993 May;46(5):450–452. doi: 10.1136/jcp.46.5.450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Colombel M., Symmans F., Gil S., O'Toole K. M., Chopin D., Benson M., Olsson C. A., Korsmeyer S., Buttyan R. Detection of the apoptosis-suppressing oncoprotein bc1-2 in hormone-refractory human prostate cancers. Am J Pathol. 1993 Aug;143(2):390–400. [PMC free article] [PubMed] [Google Scholar]
  5. Daidone M. G., Silvestrini R., Luisi A., Mastore M., Benini E., Veneroni S., Brambilla C., Ferrari L., Greco M., Andreola S. Changes in biological markers after primary chemotherapy for breast cancers. Int J Cancer. 1995 May 4;61(3):301–305. doi: 10.1002/ijc.2910610304. [DOI] [PubMed] [Google Scholar]
  6. Edwards P. D., Hurm R. A., Jaeschke W. H. Conversion of cystitis glandularis to adenocarcinoma. J Urol. 1972 Oct;108(4):568–570. doi: 10.1016/s0022-5347(17)60804-8. [DOI] [PubMed] [Google Scholar]
  7. Finke J., Lange W., Mertelsmann R., Dölken G. BCL-2 induction is part of the strategy of Epstein-Barr virus. Leuk Lymphoma. 1994 Feb;12(5-6):413–419. doi: 10.3109/10428199409073782. [DOI] [PubMed] [Google Scholar]
  8. Haldar S., Negrini M., Monne M., Sabbioni S., Croce C. M. Down-regulation of bcl-2 by p53 in breast cancer cells. Cancer Res. 1994 Apr 15;54(8):2095–2097. [PubMed] [Google Scholar]
  9. Heyns C. F., De Kock M. L., Kirsten P. H., van Velden D. J. Pelvic lipomatosis associated with cystitis glandularis and adenocarcinoma of the bladder. J Urol. 1991 Feb;145(2):364–366. doi: 10.1016/s0022-5347(17)38342-8. [DOI] [PubMed] [Google Scholar]
  10. Higashiyama M., Doi O., Kodama K., Yokouchi H., Tateishi R. High prevalence of bcl-2 oncoprotein expression in small cell lung cancer. Anticancer Res. 1995 Mar-Apr;15(2):503–505. [PubMed] [Google Scholar]
  11. Hockenbery D. M., Zutter M., Hickey W., Nahm M., Korsmeyer S. J. BCL2 protein is topographically restricted in tissues characterized by apoptotic cell death. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):6961–6965. doi: 10.1073/pnas.88.16.6961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Joensuu H., Pylkkänen L., Toikkanen S. Bcl-2 protein expression and long-term survival in breast cancer. Am J Pathol. 1994 Nov;145(5):1191–1198. [PMC free article] [PubMed] [Google Scholar]
  13. Lauwers G. Y., Scott G. V., Hendricks J. Immunohistochemical evidence of aberrant bcl-2 protein expression in gastric epithelial dysplasia. Cancer. 1994 Jun 15;73(12):2900–2904. doi: 10.1002/1097-0142(19940615)73:12<2900::aid-cncr2820731205>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  14. Lauwers G. Y., Scott G. V., Karpeh M. S. Immunohistochemical evaluation of bcl-2 protein expression in gastric adenocarcinomas. Cancer. 1995 May 1;75(9):2209–2213. doi: 10.1002/1097-0142(19950501)75:9<2209::aid-cncr2820750904>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  15. LeBrun D. P., Warnke R. A., Cleary M. L. Expression of bcl-2 in fetal tissues suggests a role in morphogenesis. Am J Pathol. 1993 Mar;142(3):743–753. [PMC free article] [PubMed] [Google Scholar]
  16. Lu P. J., Lu Q. L., Rughetti A., Taylor-Papadimitriou J. bcl-2 overexpression inhibits cell death and promotes the morphogenesis, but not tumorigenesis of human mammary epithelial cells. J Cell Biol. 1995 Jun;129(5):1363–1378. doi: 10.1083/jcb.129.5.1363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lu Q. L., Elia G., Lucas S., Thomas J. A. Bcl-2 proto-oncogene expression in Epstein-Barr-virus-associated nasopharyngeal carcinoma. Int J Cancer. 1993 Jan 2;53(1):29–35. doi: 10.1002/ijc.2910530107. [DOI] [PubMed] [Google Scholar]
  18. Lu Q. L., Poulsom R., Wong L., Hanby A. M. Bcl-2 expression in adult and embryonic non-haematopoietic tissues. J Pathol. 1993 Apr;169(4):431–437. doi: 10.1002/path.1711690408. [DOI] [PubMed] [Google Scholar]
  19. McDonnell T. J., Deane N., Platt F. M., Nunez G., Jaeger U., McKearn J. P., Korsmeyer S. J. bcl-2-immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation. Cell. 1989 Apr 7;57(1):79–88. doi: 10.1016/0092-8674(89)90174-8. [DOI] [PubMed] [Google Scholar]
  20. McDonnell T. J., Korsmeyer S. J. Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14; 18). Nature. 1991 Jan 17;349(6306):254–256. doi: 10.1038/349254a0. [DOI] [PubMed] [Google Scholar]
  21. Miyashita T., Harigai M., Hanada M., Reed J. C. Identification of a p53-dependent negative response element in the bcl-2 gene. Cancer Res. 1994 Jun 15;54(12):3131–3135. [PubMed] [Google Scholar]
  22. Miyashita T., Krajewski S., Krajewska M., Wang H. G., Lin H. K., Liebermann D. A., Hoffman B., Reed J. C. Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene. 1994 Jun;9(6):1799–1805. [PubMed] [Google Scholar]
  23. Nathan B., Anbazhagan R., Clarkson P., Bartkova J., Gusterson B. Expression of BCL-2 in the developing human fetal and infant breast. Histopathology. 1994 Jan;24(1):73–76. doi: 10.1111/j.1365-2559.1994.tb01273.x. [DOI] [PubMed] [Google Scholar]
  24. Ngan B. Y., Chen-Levy Z., Weiss L. M., Warnke R. A., Cleary M. L. Expression in non-Hodgkin's lymphoma of the bcl-2 protein associated with the t(14;18) chromosomal translocation. N Engl J Med. 1988 Jun 23;318(25):1638–1644. doi: 10.1056/NEJM198806233182502. [DOI] [PubMed] [Google Scholar]
  25. Novack D. V., Korsmeyer S. J. Bcl-2 protein expression during murine development. Am J Pathol. 1994 Jul;145(1):61–73. [PMC free article] [PubMed] [Google Scholar]
  26. Nuñez G., London L., Hockenbery D., Alexander M., McKearn J. P., Korsmeyer S. J. Deregulated Bcl-2 gene expression selectively prolongs survival of growth factor-deprived hemopoietic cell lines. J Immunol. 1990 May 1;144(9):3602–3610. [PubMed] [Google Scholar]
  27. Pezzella F., Tse A. G., Cordell J. L., Pulford K. A., Gatter K. C., Mason D. Y. Expression of the bcl-2 oncogene protein is not specific for the 14;18 chromosomal translocation. Am J Pathol. 1990 Aug;137(2):225–232. [PMC free article] [PubMed] [Google Scholar]
  28. Rowe M., Peng-Pilon M., Huen D. S., Hardy R., Croom-Carter D., Lundgren E., Rickinson A. B. Upregulation of bcl-2 by the Epstein-Barr virus latent membrane protein LMP1: a B-cell-specific response that is delayed relative to NF-kappa B activation and to induction of cell surface markers. J Virol. 1994 Sep;68(9):5602–5612. doi: 10.1128/jvi.68.9.5602-5612.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Selvakumaran M., Lin H. K., Miyashita T., Wang H. G., Krajewski S., Reed J. C., Hoffman B., Liebermann D. Immediate early up-regulation of bax expression by p53 but not TGF beta 1: a paradigm for distinct apoptotic pathways. Oncogene. 1994 Jun;9(6):1791–1798. [PubMed] [Google Scholar]
  30. Strasser A., Harris A. W., Bath M. L., Cory S. Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2. Nature. 1990 Nov 22;348(6299):331–333. doi: 10.1038/348331a0. [DOI] [PubMed] [Google Scholar]
  31. Thrasher J. B., Rajan R. R., Perez L. M., Humphrey P. A., Anderson E. E. Cystitis glandularis. Transition to adenocarcinoma of the urinary bladder. N C Med J. 1994 Nov;55(11):562–564. [PubMed] [Google Scholar]
  32. Tsujimoto Y., Finger L. R., Yunis J., Nowell P. C., Croce C. M. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science. 1984 Nov 30;226(4678):1097–1099. doi: 10.1126/science.6093263. [DOI] [PubMed] [Google Scholar]
  33. Verhaegh M. E., Sanders C. J., Arends J. W., Neumann H. A. Expression of the apoptosis-suppressing protein Bcl-2 in non-melanoma skin cancer. Br J Dermatol. 1995 May;132(5):740–744. doi: 10.1111/j.1365-2133.1995.tb00719.x. [DOI] [PubMed] [Google Scholar]
  34. Walker C., Robertson L., Myskow M., Dixon G. Expression of the BCL-2 protein in normal and dysplastic bronchial epithelium and in lung carcinomas. Br J Cancer. 1995 Jul;72(1):164–169. doi: 10.1038/bjc.1995.295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wang Y., Szekely L., Okan I., Klein G., Wiman K. G. Wild-type p53-triggered apoptosis is inhibited by bcl-2 in a v-myc-induced T-cell lymphoma line. Oncogene. 1993 Dec;8(12):3427–3431. [PubMed] [Google Scholar]
  36. Zutter M., Hockenbery D., Silverman G. A., Korsmeyer S. J. Immunolocalization of the Bcl-2 protein within hematopoietic neoplasms. Blood. 1991 Aug 15;78(4):1062–1068. [PubMed] [Google Scholar]

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