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. 2000 Oct;83(8):1033–1038. doi: 10.1054/bjoc.2000.1443

p53 expression in squamous dysplasia associated with carcinoma of the oesophagus: evidence for field carcinogenesis

M Yasuda 1, H Kuwano 2, M Watanabe 3, Y Toh 3, S Ohno 3, K Sugimachi 3
PMCID: PMC2363556  PMID: 10993651

Abstract

Squamous epithelial dysplasia is often observed multifocally in the cancerous oesophagus and is presumably considered to be a pre-cancerous lesion. A mutation of the p53 tumour suppressor gene is commonly identified in oesophageal cancer and dysplasia. p53 mutations can be anticipated immunohistochemically. In order to confirm the biological and clinical significance of p53 expressions in oesophageal field carcinogenesis, immunostaining for p53 in cancerous and multifocal precancerous lesions from resected human oesophagus was systematically investigated, while paying special attention to the contiguity of these lesions. Lesions expressing p53 were detected in 46.5% (20 of 43 lesions) of the invasive carcinoma, and in 51.0% (46 of 90 lesions) of the carcinoma in situ, and in 51.4% (92 of 179 lesions) of the dysplasia. Next, the p53 expression in dysplasia was compared with that in carcinoma for the same case. 37 of 39 (94.8%) dysplasias contiguous to p53-positive carcinomas also expressed p53 (P < 0.0001). On the other hand, the isolated dysplasias without contiguity to p53-positive carcinomas, only expressed p53 protein in 44.0% (11 of 25 lesions). No significant correlations were found between the p53 staining and either the clinicopathological features or prognosis. Discordant p53 alterations, such as those seen in cancerous and isolated precancerous lesions, may thus demonstrate further evidence for a multicentric or field carcinogenesis of the human oesophagus. © 2000 Cancer Research Campaign

Keywords: dysplasia, oesophagus, p53, immunohistochemistry, field carcinogenesis, prognosis

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Selected References

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  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. Bennett W. P., Hollstein M. C., Metcalf R. A., Welsh J. A., He A., Zhu S. M., Kusters I., Resau J. H., Trump B. F., Lane D. P. p53 mutation and protein accumulation during multistage human esophageal carcinogenesis. Cancer Res. 1992 Nov 1;52(21):6092–6097. [PubMed] [Google Scholar]
  3. Ciechanover A., DiGiuseppe J. A., Bercovich B., Orian A., Richter J. D., Schwartz A. L., Brodeur G. M. Degradation of nuclear oncoproteins by the ubiquitin system in vitro. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):139–143. doi: 10.1073/pnas.88.1.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Finlay C. A., Hinds P. W., Tan T. H., Eliyahu D., Oren M., Levine A. J. Activating mutations for transformation by p53 produce a gene product that forms an hsc70-p53 complex with an altered half-life. Mol Cell Biol. 1988 Feb;8(2):531–539. doi: 10.1128/mcb.8.2.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gao H., Wang L. D., Zhou Q., Hong J. Y., Huang T. Y., Yang C. S. p53 tumor suppressor gene mutation in early esophageal precancerous lesions and carcinoma among high-risk populations in Henan, China. Cancer Res. 1994 Aug 15;54(16):4342–4346. [PubMed] [Google Scholar]
  6. Hollstein M., Sidransky D., Vogelstein B., Harris C. C. p53 mutations in human cancers. Science. 1991 Jul 5;253(5015):49–53. doi: 10.1126/science.1905840. [DOI] [PubMed] [Google Scholar]
  7. Ikeda G., Isaji S., Chandra B., Watanabe M., Kawarada Y. Prognostic significance of biologic factors in squamous cell carcinoma of the esophagus. Cancer. 1999 Oct 15;86(8):1396–1405. doi: 10.1002/(sici)1097-0142(19991015)86:8<1396::aid-cncr3>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
  8. Kanamoto A., Kato H., Tachimori Y., Watanabe H., Nakanishi Y., Kondo H., Yamaguchi H., Gotoda T., Muro K., Matsumura Y. No prognostic significance of p53 expression in esophageal squamous cell carcinoma. J Surg Oncol. 1999 Oct;72(2):94–98. doi: 10.1002/(sici)1096-9098(199910)72:2<94::aid-jso10>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
  9. Kobayashi S., Koide Y., Endo M., Isono K., Ochiai T. The p53 gene mutation is of prognostic value in esophageal squamous cell carcinoma patients in unified stages of curability. Am J Surg. 1999 Jun;177(6):497–502. doi: 10.1016/s0002-9610(99)00085-9. [DOI] [PubMed] [Google Scholar]
  10. Koga Y., Kuwano H., Sugimachi K. Biologic characteristics of esophageal epithelial dysplasia assessed by proliferating cell nuclear antigen. Cancer. 1996 Jan 15;77(2):237–244. doi: 10.1002/(SICI)1097-0142(19960115)77:2<237::AID-CNCR3>3.0.CO;2-J. [DOI] [PubMed] [Google Scholar]
  11. Koga Y., Sugimachi K., Kuwano H., Mori M., Matsufuji H. Cytophotometric DNA analysis of esophageal dysplasia and carcinoma induced in rats by N-methyl-N-amylnitrosamine. Eur J Cancer Clin Oncol. 1988 Apr;24(4):643–651. doi: 10.1016/0277-5379(88)90294-5. [DOI] [PubMed] [Google Scholar]
  12. Kuwabara S., Ajioka Y., Watanabe H., Hitomi J., Nishikura K., Hatakeyama K. Heterogeneity of p53 mutational status in esophageal squamous cell carcinoma. Jpn J Cancer Res. 1998 Apr;89(4):405–410. doi: 10.1111/j.1349-7006.1998.tb00578.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kuwano H., Matsuda H., Matsuoka H., Kai H., Okudaira Y., Sugimachi K. Intra-epithelial carcinoma concomitant with esophageal squamous cell carcinoma. Cancer. 1987 Feb 15;59(4):783–787. doi: 10.1002/1097-0142(19870215)59:4<783::aid-cncr2820590420>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
  14. Kuwano H., Nagamatsu M., Ohno S., Matsuda H., Mori M., Sugimachi K. Coexistence of intraepithelial carcinoma and glandular differentiation in esophageal squamous cell carcinoma. Cancer. 1988 Oct 15;62(8):1568–1572. doi: 10.1002/1097-0142(19881015)62:8<1568::aid-cncr2820620818>3.0.co;2-b. [DOI] [PubMed] [Google Scholar]
  15. Kuwano H., Watanabe M., Sadanaga N., Ikebe M., Mori M., Sugimachi K. Squamous epithelial dysplasia associated with squamous cell carcinoma of the esophagus. Cancer Lett. 1993 Aug 31;72(3):141–147. doi: 10.1016/0304-3835(93)90120-x. [DOI] [PubMed] [Google Scholar]
  16. Lam K. Y., Tsao S. W., Zhang D., Law S., He D., Ma L., Wong J. Prevalence and predictive value of p53 mutation in patients with oesophageal squamous cell carcinomas: a prospective clinico-pathological study and survival analysis of 70 patients. Int J Cancer. 1997 Apr 22;74(2):212–219. doi: 10.1002/(sici)1097-0215(19970422)74:2<212::aid-ijc13>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
  17. Mori M., Adachi Y., Matsushima T., Matsuda H., Kuwano H., Sugimachi K. Lugol staining pattern and histology of esophageal lesions. Am J Gastroenterol. 1993 May;88(5):701–705. [PubMed] [Google Scholar]
  18. Morita M., Kuwano H., Yasuda M., Watanabe M., Ohno S., Saito T., Furusawa M., Sugimachi K. The multicentric occurrence of squamous epithelial dysplasia and squamous cell carcinoma in the esophagus. Cancer. 1994 Dec 1;74(11):2889–2895. doi: 10.1002/1097-0142(19941201)74:11<2889::aid-cncr2820741102>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  19. Nagamatsu M., Mori M., Kuwano H., Sugimachi K., Akiyoshi T. Serial histologic investigation of squamous epithelial dysplasia associated with carcinoma of the esophagus. Cancer. 1992 Mar 1;69(5):1094–1098. doi: 10.1002/cncr.2820690504. [DOI] [PubMed] [Google Scholar]
  20. Rogel A., Popliker M., Webb C. G., Oren M. p53 cellular tumor antigen: analysis of mRNA levels in normal adult tissues, embryos, and tumors. Mol Cell Biol. 1985 Oct;5(10):2851–2855. doi: 10.1128/mcb.5.10.2851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Shi S. T., Yang G. Y., Wang L. D., Xue Z., Feng B., Ding W., Xing E. P., Yang C. S. Role of p53 gene mutations in human esophageal carcinogenesis: results from immunohistochemical and mutation analyses of carcinomas and nearby non-cancerous lesions. Carcinogenesis. 1999 Apr;20(4):591–597. doi: 10.1093/carcin/20.4.591. [DOI] [PubMed] [Google Scholar]
  23. Shimada Y., Imamura M., Watanabe G., Uchida S., Harada H., Makino T., Kano M. Prognostic factors of oesophageal squamous cell carcinoma from the perspective of molecular biology. Br J Cancer. 1999 Jun;80(8):1281–1288. doi: 10.1038/sj.bjc.6990499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Vijeyasingam R., Darnton S. J., Jenner K., Allen C. A., Billingham C., Matthews H. R. Expression of p53 protein in oesophageal carcinoma: clinicopathological correlation and prognostic significance. Br J Surg. 1994 Nov;81(11):1623–1626. doi: 10.1002/bjs.1800811120. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. Wang L. D., Zhou Q., Hong J. Y., Qiu S. L., Yang C. S. p53 protein accumulation and gene mutations in multifocal esophageal precancerous lesions from symptom free subjects in a high incidence area for esophageal carcinoma in Henan, China. Cancer. 1996 Apr 1;77(7):1244–1249. [PubMed] [Google Scholar]
  28. Wang L. S., Chow K. C., Chi K. H., Liu C. C., Li W. Y., Chiu J. H., Huang M. H. Prognosis of esophageal squamous cell carcinoma: analysis of clinicopathological and biological factors. Am J Gastroenterol. 1999 Jul;94(7):1933–1940. doi: 10.1111/j.1572-0241.1999.01233.x. [DOI] [PubMed] [Google Scholar]
  29. van den Heuvel S. J., van Laar T., Kast W. M., Melief C. J., Zantema A., van der Eb A. J. Association between the cellular p53 and the adenovirus 5 E1B-55kd proteins reduces the oncogenicity of Ad-transformed cells. EMBO J. 1990 Aug;9(8):2621–2629. doi: 10.1002/j.1460-2075.1990.tb07444.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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