Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1995 Apr;71(4):863–867. doi: 10.1038/bjc.1995.166

Expression of tumour-suppressor gene Rb, apoptosis-suppressing protein Bcl-2 and c-Myc have no independent prognostic value in renal adenocarcinoma.

P Lipponen 1, M Eskelinen 1, K Syrjänen 1
PMCID: PMC2033746  PMID: 7710955

Abstract

The expression of retinoblastoma (Rb), c-Myc and Bcl-2 proteins was studied by immunohistochemical methods in 104 cases of renal adenocarcinoma. One tumour was completely negative for Rb protein and altered expression pattern was detected in 36% of cases. A low fraction of Rb-positive nuclei was related to high grade (P = 0.016) and high mitotic index (P = 0.012). Twenty-eight per cent of the tumours expressed c-Myc in cancer cell nuclei and 87% showed cytoplasmic positivity. Cytoplasmic expression of c-Myc was related to high grade (P = 0.002), while nuclear expression of c-Myc was related to small tumour diameter (P = 0.034), low T category (P = 0.04), low mitotic index (P = 0.019) and expression of c-ErbB-2 (P = 0.0007). Overexpression of c-myc predicted favourable outcome in M0 tumours (P = 0.0157). Bcl-2 was expressed in 20% of tumours and it was related to small tumour size (P < 0.0001), low T category (P < 0.0001), lack of venous invasion (P = 0.008), node negativity (P = 0.015) and absence of metastasis (P = 0.017). In multivariate analysis the expression of Rb, Bcl-2 and c-Myc had no independent prognostic value over T category (P < 0.001), mitotic index (P = 0.008) and combined nuclear grade (P = 0.056).

Full text

PDF
863

Images in this article

864Figure 1
on p.864

Selected References

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

  1. Allan D. J., Howell A., Roberts S. A., Williams G. T., Watson R. J., Coyne J. D., Clarke R. B., Laidlaw I. J., Potten C. S. Reduction in apoptosis relative to mitosis in histologically normal epithelium accompanies fibrocystic change and carcinoma of the premenopausal human breast. J Pathol. 1992 May;167(1):25–32. doi: 10.1002/path.1711670106. [DOI] [PubMed] [Google Scholar]
  2. Berns E. M., Klijn J. G., van Putten W. L., van Staveren I. L., Portengen H., Foekens J. A. c-myc amplification is a better prognostic factor than HER2/neu amplification in primary breast cancer. Cancer Res. 1992 Mar 1;52(5):1107–1113. [PubMed] [Google Scholar]
  3. Cordon-Cardo C., Wartinger D., Petrylak D., Dalbagni G., Fair W. R., Fuks Z., Reuter V. E. Altered expression of the retinoblastoma gene product: prognostic indicator in bladder cancer. J Natl Cancer Inst. 1992 Aug 19;84(16):1251–1256. doi: 10.1093/jnci/84.16.1251. [DOI] [PubMed] [Google Scholar]
  4. Di Silverio F., Gallucci M., Flammia G. P., De Vico A., Caponera M., Eleuteri P., Forte D., Cavallo D., De Vita R. Biological and clinical implication of cellular DNA content in renal cell carcinomas. Eur Urol. 1992;21 (Suppl 1):43–47. doi: 10.1159/000474888. [DOI] [PubMed] [Google Scholar]
  5. Doglioni C., Dei Tos A. P., Laurino L., Chiarelli C., Barbareschi M., Viale G. The prevalence of BCL-2 immunoreactivity in breast carcinomas and its clinicopathological correlates, with particular reference to oestrogen receptor status. Virchows Arch. 1994;424(1):47–51. doi: 10.1007/BF00197392. [DOI] [PubMed] [Google Scholar]
  6. Erisman M. D., Litwin S., Keidan R. D., Comis R. L., Astrin S. M. Noncorrelation of the expression of the c-myc oncogene in colorectal carcinoma with recurrence of disease or patient survival. Cancer Res. 1988 Mar 1;48(5):1350–1355. [PubMed] [Google Scholar]
  7. Eskelinen M., Lipponen P., Aitto-Oja L., Hall O., Syrjänen K. The value of histoquantitative measurements in prognostic assessment of renal adenocarcinoma. Int J Cancer. 1993 Oct 21;55(4):547–554. doi: 10.1002/ijc.2910550405. [DOI] [PubMed] [Google Scholar]
  8. Evan G. I., Littlewood T. D. The role of c-myc in cell growth. Curr Opin Genet Dev. 1993 Feb;3(1):44–49. doi: 10.1016/s0959-437x(05)80339-9. [DOI] [PubMed] [Google Scholar]
  9. Geradts J., Hu S. X., Lincoln C. E., Benedict W. F., Xu H. J. Aberrant RB gene expression in routinely processed, archival tumor tissues determined by three different anti-RB antibodies. Int J Cancer. 1994 Jul 15;58(2):161–167. doi: 10.1002/ijc.2910580203. [DOI] [PubMed] [Google Scholar]
  10. Hanada M., Krajewski S., Tanaka S., Cazals-Hatem D., Spengler B. A., Ross R. A., Biedler J. L., Reed J. C. Regulation of Bcl-2 oncoprotein levels with differentiation of human neuroblastoma cells. Cancer Res. 1993 Oct 15;53(20):4978–4986. [PubMed] [Google Scholar]
  11. Ishikawa J., Xu H. J., Hu S. X., Yandell D. W., Maeda S., Kamidono S., Benedict W. F., Takahashi R. Inactivation of the retinoblastoma gene in human bladder and renal cell carcinomas. Cancer Res. 1991 Oct 15;51(20):5736–5743. [PubMed] [Google Scholar]
  12. Kinouchi T., Saiki S., Naoe T., Uenaka A., Kotake T., Shiku H., Nakayama E. Correlation of c-myc expression with nuclear pleomorphism in human renal cell carcinoma. Cancer Res. 1989 Jul 1;49(13):3627–3630. [PubMed] [Google Scholar]
  13. Koskinen P. J., Alitalo K. Role of myc amplification and overexpression in cell growth, differentiation and death. Semin Cancer Biol. 1993 Feb;4(1):3–12. [PubMed] [Google Scholar]
  14. Kotake T., Saiki S., Kinouchi T., Shiku H., Nakayama E. Detection of the c-myc gene product in urinary bladder cancer. Jpn J Cancer Res. 1990 Dec;81(12):1198–1201. doi: 10.1111/j.1349-7006.1990.tb02677.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lanigan D., McLean P. A., Murphy D. M., Donovan M. G., Curran B., Leader M. c-myc expression in renal carcinoma: correlation with clinical parameters. Br J Urol. 1993 Aug;72(2):143–147. doi: 10.1111/j.1464-410x.1993.tb00675.x. [DOI] [PubMed] [Google Scholar]
  16. Lee E. T., Desu M. M. A computer program for comparing K samples with right-censored data. Comput Programs Biomed. 1972 Nov;2(4):315–321. doi: 10.1016/0010-468x(72)90019-0. [DOI] [PubMed] [Google Scholar]
  17. Lipponen P., Eskelinen M., Hietala K., Syrjänen K., Gambetta R. A. Expression of proliferating cell nuclear antigen (PC10), p53 protein and c-erbB-2 in renal adenocarcinoma. Int J Cancer. 1994 Apr 15;57(2):275–280. doi: 10.1002/ijc.2910570224. [DOI] [PubMed] [Google Scholar]
  18. Logothetis C. J., Xu H. J., Ro J. Y., Hu S. X., Sahin A., Ordonez N., Benedict W. F. Altered expression of retinoblastoma protein and known prognostic variables in locally advanced bladder cancer. J Natl Cancer Inst. 1992 Aug 19;84(16):1256–1261. doi: 10.1093/jnci/84.16.1256. [DOI] [PubMed] [Google Scholar]
  19. Makos M., Nelkin B. D., Reiter R. E., Gnarra J. R., Brooks J., Isaacs W., Linehan M., Baylin S. B. Regional DNA hypermethylation at D17S5 precedes 17p structural changes in the progression of renal tumors. Cancer Res. 1993 Jun 15;53(12):2719–2722. [PubMed] [Google Scholar]
  20. Melhem M. F., Meisler A. I., Finley G. G., Bryce W. H., Jones M. O., Tribby I. I., Pipas J. M., Koski R. A. Distribution of cells expressing myc proteins in human colorectal epithelium, polyps, and malignant tumors. Cancer Res. 1992 Nov 1;52(21):5853–5864. [PubMed] [Google Scholar]
  21. Münzel P., Marx D., Köchel H., Schauer A., Bock K. W. Genomic alterations of the c-myc protooncogene in relation to the overexpression of c-erbB2 and Ki-67 in human breast and cervix carcinomas. J Cancer Res Clin Oncol. 1991;117(6):603–607. doi: 10.1007/BF01613296. [DOI] [PubMed] [Google Scholar]
  22. Nguyen M., Millar D. G., Yong V. W., Korsmeyer S. J., Shore G. C. Targeting of Bcl-2 to the mitochondrial outer membrane by a COOH-terminal signal anchor sequence. J Biol Chem. 1993 Dec 5;268(34):25265–25268. [PubMed] [Google Scholar]
  23. Ogawa O., Habuchi T., Kakehi Y., Koshiba M., Sugiyama T., Yoshida O. Allelic losses at chromosome 17p in human renal cell carcinoma are inversely related to allelic losses at chromosome 3p. Cancer Res. 1992 Apr 1;52(7):1881–1885. [PubMed] [Google Scholar]
  24. Sachs L., Lotem J. Control of programmed cell death in normal and leukemic cells: new implications for therapy. Blood. 1993 Jul 1;82(1):15–21. [PubMed] [Google Scholar]
  25. Sawan A., Randall B., Angus B., Wright C., Henry J. A., Ostrowski J., Hennessy C., Lennard T. W., Corbett I., Horne C. H. Retinoblastoma and p53 gene expression related to relapse and survival in human breast cancer: an immunohistochemical study. J Pathol. 1992 Sep;168(1):23–28. doi: 10.1002/path.1711680105. [DOI] [PubMed] [Google Scholar]
  26. Schena M., Gottardi D., Ghia P., Larsson L. G., Carlsson M., Nilsson K., Caligaris-Cappio F. The role of Bcl-2 in the pathogenesis of B chronic lymphocytic leukemia. Leuk Lymphoma. 1993 Oct;11(3-4):173–179. doi: 10.3109/10428199309086993. [DOI] [PubMed] [Google Scholar]
  27. Silvestrini R., Benini E., Daidone M. G., Veneroni S., Boracchi P., Cappelletti V., Di Fronzo G., Veronesi U. p53 as an independent prognostic marker in lymph node-negative breast cancer patients. J Natl Cancer Inst. 1993 Jun 16;85(12):965–970. doi: 10.1093/jnci/85.12.965. [DOI] [PubMed] [Google Scholar]
  28. Syrjänen K., Hjelt L. Grading of human renal adenocarcinoma. Scand J Urol Nephrol. 1978;12(1):49–55. [PubMed] [Google Scholar]
  29. Syrjänen K., Hjelt L. Ultrastructural characteristics of human renal cell carcinoma in relation to the light microscopic grading. Scand J Urol Nephrol. 1978;12(1):57–65. [PubMed] [Google Scholar]
  30. Tal M., Wetzler M., Josefberg Z., Deutch A., Gutman M., Assaf D., Kris R., Shiloh Y., Givol D., Schlessinger J. Sporadic amplification of the HER2/neu protooncogene in adenocarcinomas of various tissues. Cancer Res. 1988 Mar 15;48(6):1517–1520. [PubMed] [Google Scholar]
  31. Waitz W., Loidl P. Cell cycle dependent association of c-myc protein with the nuclear matrix. Oncogene. 1991 Jan;6(1):29–35. [PubMed] [Google Scholar]
  32. Xu H. J., Cairns P., Hu S. X., Knowles M. A., Benedict W. F. Loss of RB protein expression in primary bladder cancer correlates with loss of heterozygosity at the RB locus and tumor progression. Int J Cancer. 1993 Mar 12;53(5):781–784. doi: 10.1002/ijc.2910530513. [DOI] [PubMed] [Google Scholar]
  33. Yamaguchi A., Ninomiya I., Ishida T., Nishimura G., Kanno M., Yonemura Y., Miwa K., Miyazaki I., Matsukawa S. Immunohistochemical detection of c-myc products in colorectal cancer and proliferative cell rate. Oncology. 1992;49(1):40–44. doi: 10.1159/000227008. [DOI] [PubMed] [Google Scholar]
  34. de Jong D., Prins F. A., Mason D. Y., Reed J. C., van Ommen G. B., Kluin P. M. Subcellular localization of the bcl-2 protein in malignant and normal lymphoid cells. Cancer Res. 1994 Jan 1;54(1):256–260. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES