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

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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

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References

  1. Bennett WP, Hollstein MC, He A, Zhu SM, Resau J, Trump BF, Metcalf RA, Welsh JA, Midgley C, Lane DP and Harris CC (1991) Archival analysis of p53 genetic and protein alterations in Chinese esophageal cancer. Oncogene 6: 1779–1784

  2. Bennett WP, Hollstein MC, Metcalf RA, Welsh JA, He A, Zhu SM, Kusters I, Resau JH, Trump BF, Lane DP and Harris CC (1992) p53 mutation and protein accumulation during multistage human esophageal carcinogenesis. Cancer Res 52: 6092–6097

  3. Ciechanover A, DiGiuseppe JA, Bercovich B, Orian A, Richter JD, Schwartz AL and Brodeur GM (1991) Degradation of nuclear oncoproteins by the ubiquitin system in vitro. Proc Natl Acad Sci USA 88: 139–143

  4. Finlay CA, Hinds PW, Tan TH, Eliyahu D, Oren M and Levine AJ (1988) Activating mutations for transformation by p53 produce a gene product that forms an hsc70–p53 complex with an altered half-life. Mol Cell Biol 8: 531–539

  5. Gao H, Wang LD, Zhou Q, Hong JY, Huang TY and Yang CS (1994) p53 tumour suppressor gene mutation in early esophageal precancerous lesions and carcinoma among high-risk populations in Henan, China. Cancer Res 54: 4342–4346

  6. Hall PA and Lane DP (1994) p53 in tumour pathology: can we trust immunohistochemistry? revisited. J Pathol 172: 1–4

  7. Hollstein M, Sidransky D, Vogelstein B and Harris CC (1991) p53 mutations in human cancers. Science 253: 49–53

  8. Ikeda G, Isaji S, Chandra B, Watanabe M and Kawarada Y (1999) Prognostic significance of biologic factors in squamous cell carcinoma of the esophagus. Cancer 86: 1396–1405

  9. Kanamoto A, Kato H, Tachimori Y, Watanabe H, Nakanishi Y, Kondo H, Yamaguchi H, Gotoda T, Muro K and Matsumura Y (1999) No prognostic significance of p53 expression in esophageal squamous cell carcinoma. J Surg Oncol 72: 94–98

  10. Kawabara S, Ajioka Y, Watanabe H, Hitomi J, Nishikura K and Hatakeyama K (1998) Heterogeneity of p53 mutational status in esophageal squamous cell carcinoma. Jpn J Cancer Res 89: 405–410

  11. Kobayashi S, Koide Y, Endo M, Isono K and Ochiai T (1999) The p53 gene mutation is of prognostic value in esophageal squamous cell carcinoma patients in unified stages of curability. Am J Surg 177: 497–502

  12. Koga Y, Sugimachi K, Kuwano H, Mori M and Matsufuji H (1988) Cytophotometric DNA analysis of esophageal dysplasia and carcinoma induced in rats by N-methyl-N-amylnitrosamine. Eur J Cancer Clin Oncol 24: 643–651

  13. Koga Y, Kuwano H and Sugimachi K (1996) Biologic characteristics of esophageal epithelial dysplasia assessed by proliferating cell nuclear antigen. Cancer 77: 237–244

  14. Kuwano H, Matsuda H, Matsuoka H, Kai H, Okudaira Y and Sugimachi K (1987) Intra-epithelial carcinoma concomitant with esophageal squamous cell carcinoma. Cancer 59: 783–787

  15. Kuwano H, Nagamatsu M, Ohno S, Matsuda H, Mori M and Sugimachi K (1988) Coexistence of intraepithelial carcinoma and glandular differentiation in esophageal squamous cell carcinoma. Cancer 62: 1568–1572

  16. Kuwano H, Watanabe M, Sadanaga N, Ikebe M, Mori M and Sugimachi K (1993) Squamous epithelial dysplasia associated with squamous cell carcinoma of the esophagus. Cancer Lett 72: 141–147

  17. Lam KY, Tsao SW, Zhang D, Law S, He D, Ma L and Wong J (1997) 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 74: 212–219

  18. Mori M, Adachi Y, Matsushima T, Matsuda H, Kuwano H and Sugimachi K (1993) Lugol staining pattern and histology of esophageal lesions. Am J Gastroenterol 88: 701–705

  19. Morita M, Kuwano H, Yasuda M, Watanabe M, Ohno S, Saito T, Furusawa M and Sugimachi K (1994) The multicentric occurrence of squamous epithelial dysplasia and squamous cell carcinoma in the esophagus. Cancer 74: 2889–2895

  20. Nagamatsu M, Mori M, Kuwano H, Sugimachi K and Akiyoshi T (1992) Serial histologic investigation of squamous epithelial dysplasia associated with carcinoma of the esophagus. Cancer 69: 1094–1098

  21. Rogel A, Popliker M, Webb CG and Oren M (1985) p53 cellular tumour antigen: Analysis of mRNA levels in normal adult tissues, embryos and tumours. Mol Cell Biol 5: 2851–2855

  22. Sarbia M, Porschen R, Borchard F, Horstmann O, Willers R and Gabbert HE (1994) p53 protein expression and prognosis in squamous cell carcinoma of the esophagus. Cancer 74: 2218–2223

  23. Shi ST, Yang GY, Wang LD, Xue Z, Feng B, Ding W, Xing EP and Yang CS (1999) Role of p53 gene mutations in human esophageal carcinogenesis: results from immunohistochemical and mutation analyses of carcinomas and nearby noncancerous lesions. Carcinogenesis 20: 591–597

  24. Shimada Y, Imamura M, Watanabe G, Uchida S, Harada H, Makino T and Kano M (1999) Prognostic factors of oesophageal squamous cell carcinoma from the perspective of molecular biology. Br J Cancer 80: 1281–1288

  25. Sobin LH and Wittekind CH (1997). TNM Classification of Malignant Tumours, 5th edn, Wiley-Liss: New York

  26. Tsutsui S, Kuwano H, Yasuda M, Nozoe T, Watanabe M, Kitamura M and Sugimachi K (1995) Extensive spreading carcinoma of the esophagus with invasion restricted to the submucosa. Am J Gastroenterol 90: 308–313

  27. van den Heuvel SJL, van Laar T, Kast WM, Melief CJM, Zantema A and van der Eb AJ (1990) Association between the cellular p53 and the adenovirus 5 E1B-55kd proteins reduces the oncogenicity of Ad-transformed cells. EMBO J 8: 2621–2629

  28. Vijeyasingam R, Darnton SJ, Jenner K, Allen CA, Billingham C and Matthews HR (1994) Expression of p53 protein in oesophageal carcinoma: clinicopathological correlation and prognostic significance. Br J Surg 81: 1623–1626

  29. Wagata T, Shibagaki I, Imamura M, Shimada Y, Toguchida J, Yandell DW, Ikenaga M, Tobe T and Ishizaki K (1993) Loss of 17p, mutation of p53 gene, and overexpression of p53 protein in esophageal squamous cell carcinomas. Cancer Res 53: 846–850

  30. Wang LD, Hong JY, Qiu SL, Gao H and Yang CS (1993) Accumulation of p53 protein in human esophageal precancerous lesions: a possible early biomarker for carcinogenesis. Cancer Res 53: 1783–1787

  31. Wang LD, Zhou Q, Hong JY, Qiu SL and Yang CS (1996) 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 77: 1244–1249

  32. Wang LS, Chow KC, Chi KH, Liu CC, Li WY, Chiu JH and Huang MH (1999) Prognosis of esophageal squamous cell carcinoma: analysis of clinicopathological and biological factors. Am J Gastroenterol 94: 1933–1940

  33. Watanabe H, Jass JR and Solin L (1990). Histological typing of oesophageal and gastric tumours 2nd edn. pp 11–18, Springer-Verlag: Berlin, Heidelberg, New York, London, Paris, Tokyo, Hong Kong

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Yasuda, M., Kuwano, H., Watanabe, M. et al. p53 expression in squamous dysplasia associated with carcinoma of the oesophagus: evidence for field carcinogenesis. Br J Cancer 83, 1033–1038 (2000) doi:10.1054/bjoc.2000.1443

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Keywords

  • dysplasia
  • oesophagus
  • p53
  • immunohistochemistry
  • field carcinogenesis
  • prognosis

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