Skip to main content
NCBI home page
Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1996 Jun;49(6):456–459. doi: 10.1136/jcp.49.6.456

Expression of p53 and bcl-2 and response to preoperative chemotherapy and radiotherapy for locally advanced squamous cell carcinoma of the oesophagus.

F Puglisi 1, C Di Loreto 1, R Panizzo 1, C Avellini 1, S Fongione 1, V Cacitti 1, C A Beltrami 1
PMCID: PMC500533  PMID: 8763257

Abstract

AIMS: To investigate the immunohistochemical expression of p53 and bcl-2 proteins in squamous cell carcinoma (SCC) of the oesophagus and to assess whether expression of these oncoproteins can be used to stratify patients into groups with a favourable or unfavourable response to preoperative chemo/radiotherapy. METHODS: The initial diagnostic biopsy and the corresponding resected samples were obtained from 22 consecutive patients with SCC. All patients underwent preoperative chemo/radiotherapy. Tumour sections were incubated with a monoclonal antibody directed against p53 (DO-7). Twenty four non-neoplastic oesophageal biopsy specimens immunostained for p53 served as controls. Twelve randomly chosen sections from the 22 SCC samples were immunostained to test for bcl-2 protein expression. RESULTS: After chemo/radiotherapy, 12 (55%) of the 22 patients had no evidence of tumour in the resected oesophagus. Before chemoradiotherapy, however, 17 (77%) patients were p53 positive. After treatment, residual carcinoma was detected in seven (41%) of the 17 p53 positive patients. All non-responsive cases had the same p53 immunopattern as before treatment. Bcl-2 immunoexpression was detected in six (50%) of 12 patients. Residual tumour was detected in the residual oesophagus in two (33%) of the six bcl-2 positive patients. After treatment, bcl-2 expression was no longer detected in the residual neoplastic cells of a previously bcl-2 positive tumour. Using Fisher's exact test no significant association was found between oncoprotein expression and response to preoperative treatment. CONCLUSION: This study confirms the observation that p53 protein is frequently expressed in SCCs of the oesophagus, probably as a result of a mutation of the TP53 gene. However, no significant association was found between oncoprotein expression and response to chemo/radiotherapy. Anticancer agents do not seem to modify the expression of p53 and bcl-2 proteins.

Full text

PDF
456

Images in this article

457Image
on p.457
457Image
on p.457
457Image
on p.457

Selected References

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

  1. Bennett W. P., Hollstein M. C., He A., Zhu S. M., Resau J. H., Trump B. F., Metcalf R. A., Welsh J. A., Midgley C., Lane D. P. Archival analysis of p53 genetic and protein alterations in Chinese esophageal cancer. Oncogene. 1991 Oct;6(10):1779–1784. [PubMed] [Google Scholar]
  2. Chiou S. K., Rao L., White E. Bcl-2 blocks p53-dependent apoptosis. Mol Cell Biol. 1994 Apr;14(4):2556–2563. doi: 10.1128/mcb.14.4.2556. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Hall P. A., McKee P. H., Menage H. D., Dover R., Lane D. P. High levels of p53 protein in UV-irradiated normal human skin. Oncogene. 1993 Jan;8(1):203–207. [PubMed] [Google Scholar]
  4. Kastan M. B., Onyekwere O., Sidransky D., Vogelstein B., Craig R. W. Participation of p53 protein in the cellular response to DNA damage. Cancer Res. 1991 Dec 1;51(23 Pt 1):6304–6311. [PubMed] [Google Scholar]
  5. Kerr J. F., Winterford C. M., Harmon B. V. Apoptosis. Its significance in cancer and cancer therapy. Cancer. 1994 Apr 15;73(8):2013–2026. doi: 10.1002/1097-0142(19940415)73:8<2013::aid-cncr2820730802>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  6. Kerr J. F., Wyllie A. H., Currie A. R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972 Aug;26(4):239–257. doi: 10.1038/bjc.1972.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kinzler K. W., Vogelstein B. Cancer therapy meets p53. N Engl J Med. 1994 Jul 7;331(1):49–50. doi: 10.1056/NEJM199407073310113. [DOI] [PubMed] [Google Scholar]
  8. Lane D. P. Cancer. p53, guardian of the genome. Nature. 1992 Jul 2;358(6381):15–16. doi: 10.1038/358015a0. [DOI] [PubMed] [Google Scholar]
  9. Levine A. J., Perry M. E., Chang A., Silver A., Dittmer D., Wu M., Welsh D. The 1993 Walter Hubert Lecture: the role of the p53 tumour-suppressor gene in tumorigenesis. Br J Cancer. 1994 Mar;69(3):409–416. doi: 10.1038/bjc.1994.76. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lowe S. W., Bodis S., McClatchey A., Remington L., Ruley H. E., Fisher D. E., Housman D. E., Jacks T. p53 status and the efficacy of cancer therapy in vivo. Science. 1994 Nov 4;266(5186):807–810. doi: 10.1126/science.7973635. [DOI] [PubMed] [Google Scholar]
  11. Lowe S. W., Ruley H. E., Jacks T., Housman D. E. p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell. 1993 Sep 24;74(6):957–967. doi: 10.1016/0092-8674(93)90719-7. [DOI] [PubMed] [Google Scholar]
  12. McIlwrath A. J., Vasey P. A., Ross G. M., Brown R. Cell cycle arrests and radiosensitivity of human tumor cell lines: dependence on wild-type p53 for radiosensitivity. Cancer Res. 1994 Jul 15;54(14):3718–3722. [PubMed] [Google Scholar]
  13. Merritt A. J., Potten C. S., Kemp C. J., Hickman J. A., Balmain A., Lane D. P., Hall P. A. The role of p53 in spontaneous and radiation-induced apoptosis in the gastrointestinal tract of normal and p53-deficient mice. Cancer Res. 1994 Feb 1;54(3):614–617. [PubMed] [Google Scholar]
  14. Miyashita T., Reed J. C. Bcl-2 oncoprotein blocks chemotherapy-induced apoptosis in a human leukemia cell line. Blood. 1993 Jan 1;81(1):151–157. [PubMed] [Google Scholar]
  15. O'Connor P. M., Jackman J., Jondle D., Bhatia K., Magrath I., Kohn K. W. Role of the p53 tumor suppressor gene in cell cycle arrest and radiosensitivity of Burkitt's lymphoma cell lines. Cancer Res. 1993 Oct 15;53(20):4776–4780. [PubMed] [Google Scholar]
  16. Sarbia M., Porschen R., Borchard F., Horstmann O., Willers R., Gabbert H. E. p53 protein expression and prognosis in squamous cell carcinoma of the esophagus. Cancer. 1994 Oct 15;74(8):2218–2223. doi: 10.1002/1097-0142(19941015)74:8<2218::aid-cncr2820740803>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  17. Steller H. Mechanisms and genes of cellular suicide. Science. 1995 Mar 10;267(5203):1445–1449. doi: 10.1126/science.7878463. [DOI] [PubMed] [Google Scholar]
  18. Stewart B. W. Mechanisms of apoptosis: integration of genetic, biochemical, and cellular indicators. J Natl Cancer Inst. 1994 Sep 7;86(17):1286–1296. doi: 10.1093/jnci/86.17.1286. [DOI] [PubMed] [Google Scholar]
  19. Volant A., Nousbaum J. B., Giroux M. A., Roué-Quintin I., Metges J. P., Férec C., Gouérou H., Robaszkiewicz M. p53 protein accumulation in oesophageal squamous cell carcinomas and precancerous lesions. J Clin Pathol. 1995 Jun;48(6):531–534. doi: 10.1136/jcp.48.6.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wagata T., Shibagaki I., Imamura M., Shimada Y., Toguchida J., Yandell D. W., Ikenaga M., Tobe T., Ishizaki K. Loss of 17p, mutation of the p53 gene, and overexpression of p53 protein in esophageal squamous cell carcinomas. Cancer Res. 1993 Feb 15;53(4):846–850. [PubMed] [Google Scholar]
  21. Wang L. D., Hong J. Y., Qiu S. L., Gao H., Yang C. S. Accumulation of p53 protein in human esophageal precancerous lesions: a possible early biomarker for carcinogenesis. Cancer Res. 1993 Apr 15;53(8):1783–1787. [PubMed] [Google Scholar]

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Publishing Group

RESOURCES