Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1998;77(1):92–97. doi: 10.1038/bjc.1998.14

Cyclin D1 overexpression related to retinoblastoma protein expression as a prognostic marker in human oesophageal squamous cell carcinoma.

T Ishikawa 1, M Furihata 1, Y Ohtsuki 1, H Murakami 1, A Inoue 1, S Ogoshi 1
PMCID: PMC2151245  PMID: 9459151

Abstract

The relationship between aberrant expression of cyclin D1 and retinoblastoma (RB) protein and clinicopathological factors was investigated in 80 patients with oesophageal SCC using immunohistochemical analyses. Heterogeneous staining of cancer cell nuclei with antibody to cyclin D1 was found in 31.3% of patients (25 out of 80 patients). Nuclear staining of cancer cells with anti-RB antibody was homogeneous in 10.0% (8 out of 80 patients) and heterogeneous in 58.8% (47 out of 80 patients). Among cases with homogeneous staining for RB protein, 75% (six out of eight patients) exhibited simultaneous positivity for cyclin D1 (P < 0.05). No significant relationship was found between cyclin D1 or RB protein expression and various clinicopathological parameters. The prognosis of patients with cyclin D1-positive tumours was significantly poorer than that of the other patients (P < 0.01). In addition, when patients with cyclin D1-positive and -negative tumours were stratified according to presence or absence of lymph node metastasis and RB status, the cumulative survival rates in the cyclin D1-positive groups were significantly lower for patients without lymph node metastasis (P < 0.01) and for patients whose tumours were positive for RB (P< 0.0001). These findings suggest the possibility that cyclin D1 positivity is a useful prognostic marker related to lymph node metastasis and RB protein expression in human oesophageal SCC, in addition to clinicopathological factors.

Full text

PDF
92

Images in this article

93Figure 1
on p.93
93Figure 2
on p.93

Selected References

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

  1. Adélaide J., Monges G., Dérdérian C., Seitz J. F., Birnbaum D. Oesophageal cancer and amplification of the human cyclin D gene CCND1/PRAD1. Br J Cancer. 1995 Jan;71(1):64–68. doi: 10.1038/bjc.1995.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Buckley M. F., Sweeney K. J., Hamilton J. A., Sini R. L., Manning D. L., Nicholson R. I., deFazio A., Watts C. K., Musgrove E. A., Sutherland R. L. Expression and amplification of cyclin genes in human breast cancer. Oncogene. 1993 Aug;8(8):2127–2133. [PubMed] [Google Scholar]
  3. Cordon-Cardo C. Mutations of cell cycle regulators. Biological and clinical implications for human neoplasia. Am J Pathol. 1995 Sep;147(3):545–560. [PMC free article] [PubMed] [Google Scholar]
  4. Ewen M. E., Sluss H. K., Sherr C. J., Matsushime H., Kato J., Livingston D. M. Functional interactions of the retinoblastoma protein with mammalian D-type cyclins. Cell. 1993 May 7;73(3):487–497. doi: 10.1016/0092-8674(93)90136-e. [DOI] [PubMed] [Google Scholar]
  5. Fahn H. J., Wang L. S., Huang B. S., Huang M. H., Chien K. Y. Tumor recurrence in long-term survivors after treatment of carcinoma of the esophagus. Ann Thorac Surg. 1994 Mar;57(3):677–681. doi: 10.1016/0003-4975(94)90566-5. [DOI] [PubMed] [Google Scholar]
  6. Furihata M., Ishikawa T., Inoue A., Yoshikawa C., Sonobe H., Ohtsuki Y., Araki K., Ogoshi S. Determination of the prognostic significance of unscheduled cyclin A overexpression in patients with esophageal squamous cell carcinoma. Clin Cancer Res. 1996 Oct;2(10):1781–1785. [PubMed] [Google Scholar]
  7. Furihata M., Ohtsuki Y., Ogoshi S., Takahashi A., Tamiya T., Ogata T. Prognostic significance of human papillomavirus genomes (type-16, -18) and aberrant expression of p53 protein in human esophageal cancer. Int J Cancer. 1993 May 8;54(2):226–230. doi: 10.1002/ijc.2910540211. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Gillett C., Fantl V., Smith R., Fisher C., Bartek J., Dickson C., Barnes D., Peters G. Amplification and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining. Cancer Res. 1994 Apr 1;54(7):1812–1817. [PubMed] [Google Scholar]
  10. Gong J., Ardelt B., Traganos F., Darzynkiewicz Z. Unscheduled expression of cyclin B1 and cyclin E in several leukemic and solid tumor cell lines. Cancer Res. 1994 Aug 15;54(16):4285–4288. [PubMed] [Google Scholar]
  11. Hunter T., Pines J. Cyclins and cancer. II: Cyclin D and CDK inhibitors come of age. Cell. 1994 Nov 18;79(4):573–582. doi: 10.1016/0092-8674(94)90543-6. [DOI] [PubMed] [Google Scholar]
  12. Hunter T., Pines J. Cyclins and cancer. Cell. 1991 Sep 20;66(6):1071–1074. doi: 10.1016/0092-8674(91)90028-w. [DOI] [PubMed] [Google Scholar]
  13. Jares P., Fernández P. L., Campo E., Nadal A., Bosch F., Aiza G., Nayach I., Traserra J., Cardesa A. PRAD-1/cyclin D1 gene amplification correlates with messenger RNA overexpression and tumor progression in human laryngeal carcinomas. Cancer Res. 1994 Sep 1;54(17):4813–4817. [PubMed] [Google Scholar]
  14. Jiang W., Zhang Y. J., Kahn S. M., Hollstein M. C., Santella R. M., Lu S. H., Harris C. C., Montesano R., Weinstein I. B. Altered expression of the cyclin D1 and retinoblastoma genes in human esophageal cancer. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9026–9030. doi: 10.1073/pnas.90.19.9026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kato H., Tachimori Y., Watanabe H., Iizuka T. Evaluation of the new (1987) TNM classification for thoracic esophageal tumors. Int J Cancer. 1993 Jan 21;53(2):220–223. doi: 10.1002/ijc.2910530208. [DOI] [PubMed] [Google Scholar]
  16. Kato H., Tachimori Y., Watanabe H., Iizuka T., Terui S., Itabashi M., Hirota T. Lymph node metastasis in thoracic esophageal carcinoma. J Surg Oncol. 1991 Oct;48(2):106–111. doi: 10.1002/jso.2930480207. [DOI] [PubMed] [Google Scholar]
  17. Keyomarsi K., O'Leary N., Molnar G., Lees E., Fingert H. J., Pardee A. B. Cyclin E, a potential prognostic marker for breast cancer. Cancer Res. 1994 Jan 15;54(2):380–385. [PubMed] [Google Scholar]
  18. Lipponen P. K., Liukkonen T. J. Reduced expression of retinoblastoma (Rb) gene protein is related to cell proliferation and prognosis in transitional-cell bladder cancer. J Cancer Res Clin Oncol. 1995;121(1):44–50. doi: 10.1007/BF01202728. [DOI] [PubMed] [Google Scholar]
  19. Matsushime H., Quelle D. E., Shurtleff S. A., Shibuya M., Sherr C. J., Kato J. Y. D-type cyclin-dependent kinase activity in mammalian cells. Mol Cell Biol. 1994 Mar;14(3):2066–2076. doi: 10.1128/mcb.14.3.2066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. McIntosh G. G., Anderson J. J., Milton I., Steward M., Parr A. H., Thomas M. D., Henry J. A., Angus B., Lennard T. W., Horne C. H. Determination of the prognostic value of cyclin D1 overexpression in breast cancer. Oncogene. 1995 Sep 7;11(5):885–891. [PubMed] [Google Scholar]
  21. Michalides R., van Veelen N., Hart A., Loftus B., Wientjens E., Balm A. Overexpression of cyclin D1 correlates with recurrence in a group of forty-seven operable squamous cell carcinomas of the head and neck. Cancer Res. 1995 Mar 1;55(5):975–978. [PubMed] [Google Scholar]
  22. Motokura T., Bloom T., Kim H. G., Jüppner H., Ruderman J. V., Kronenberg H. M., Arnold A. A novel cyclin encoded by a bcl1-linked candidate oncogene. Nature. 1991 Apr 11;350(6318):512–515. doi: 10.1038/350512a0. [DOI] [PubMed] [Google Scholar]
  23. Müller H., Lukas J., Schneider A., Warthoe P., Bartek J., Eilers M., Strauss M. Cyclin D1 expression is regulated by the retinoblastoma protein. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):2945–2949. doi: 10.1073/pnas.91.8.2945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Naitoh H., Shibata J., Kawaguchi A., Kodama M., Hattori T. Overexpression and localization of cyclin D1 mRNA and antigen in esophageal cancer. Am J Pathol. 1995 May;146(5):1161–1169. [PMC free article] [PubMed] [Google Scholar]
  25. Pagano M., Pepperkok R., Verde F., Ansorge W., Draetta G. Cyclin A is required at two points in the human cell cycle. EMBO J. 1992 Mar;11(3):961–971. doi: 10.1002/j.1460-2075.1992.tb05135.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sherr C. J. Mammalian G1 cyclins. Cell. 1993 Jun 18;73(6):1059–1065. doi: 10.1016/0092-8674(93)90636-5. [DOI] [PubMed] [Google Scholar]
  27. Shew J. Y., Ling N., Yang X. M., Fodstad O., Lee W. H. Antibodies detecting abnormalities of the retinoblastoma susceptibility gene product (pp110RB) in osteosarcomas and synovial sarcomas. Oncogene Res. 1989;4(3):205–214. [PubMed] [Google Scholar]
  28. Shimaya K., Shiozaki H., Inoue M., Tahara H., Monden T., Shimano T., Mori T. Significance of p53 expression as a prognostic factor in oesophageal squamous cell carcinoma. Virchows Arch A Pathol Anat Histopathol. 1993;422(4):271–276. doi: 10.1007/BF01608335. [DOI] [PubMed] [Google Scholar]
  29. Shinozaki H., Ozawa S., Ando N., Tsuruta H., Terada M., Ueda M., Kitajima M. Cyclin D1 amplification as a new predictive classification for squamous cell carcinoma of the esophagus, adding gene information. Clin Cancer Res. 1996 Jul;2(7):1155–1161. [PubMed] [Google Scholar]
  30. Trudel M., Mulligan L., Cavenee W., Margolese R., Côté J., Gariépy G. Retinoblastoma and p53 gene product expression in breast carcinoma: immunohistochemical analysis and clinicopathologic correlation. Hum Pathol. 1992 Dec;23(12):1388–1394. doi: 10.1016/0046-8177(92)90059-c. [DOI] [PubMed] [Google Scholar]
  31. Tsuruta H., Sakamoto H., Onda M., Terada M. Amplification and overexpression of EXP1 and EXP2/Cyclin D1 genes in human esophageal carcinomas. Biochem Biophys Res Commun. 1993 Nov 15;196(3):1529–1536. doi: 10.1006/bbrc.1993.2425. [DOI] [PubMed] [Google Scholar]
  32. Weinberg R. A. Tumor suppressor genes. Science. 1991 Nov 22;254(5035):1138–1146. doi: 10.1126/science.1659741. [DOI] [PubMed] [Google Scholar]
  33. Xu H. J., Hu S. X., Benedict W. F. Lack of nuclear RB protein staining in G0/middle G1 cells: correlation to changes in total RB protein level. Oncogene. 1991 Jul;6(7):1139–1146. [PubMed] [Google Scholar]
  34. Xu H. J., Hu S. X., Hashimoto T., Takahashi R., Benedict W. F. The retinoblastoma susceptibility gene product: a characteristic pattern in normal cells and abnormal expression in malignant cells. Oncogene. 1989 Jun;4(6):807–812. [PubMed] [Google Scholar]
  35. Zhang Y. J., Jiang W., Chen C. J., Lee C. S., Kahn S. M., Santella R. M., Weinstein I. B. Amplification and overexpression of cyclin D1 in human hepatocellular carcinoma. Biochem Biophys Res Commun. 1993 Oct 29;196(2):1010–1016. doi: 10.1006/bbrc.1993.2350. [DOI] [PubMed] [Google Scholar]

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

RESOURCES