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p53 Accumulation Is a Prognostic Factor in Intestinal-Type Gastric Carcinoma but Not in the Diffuse Type

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Abstract

Background: The prognostic value of p53 nuclear accumulation in gastric cancer is still unclear, as shown by the discordant results still reported in the literature. In this study, we evaluated the correlation between p53 accumulation and long-term survival of patients resected for intestinal and diffuse-type gastric cancer.

Methods: Eighty-three patients with carcinoma of the intestinal type and 53 patients with carcinoma of the diffuse type were included in the study. Immunohistochemical staining of the paraffin sections was performed by using monoclonal antibody DO1; cases were considered positive when nuclear immunostaining was observed in 10% or more of the tumor cells. Prognostic significance of different variables was investigated by univariate and multivariate analysis.

Results: p53 positivity was found in 51.8% of intestinal-type and 50.9% of diffuse-type cases. No significant correlation between the rate of p53 overexpression and age, sex, tumor location, tumor size, depth of invasion, lymph node involvement, distant metastases, and surgical radicality was found in the two groups of patients. A statistically significant difference in survival rate was observed between p53-negative and p53-positive cases in the intestinal type (P < .05), confirmed by multivariate analysis (P < .005; relative risk = 3.09). On the contrary, no correlation with survival was found in diffuse-type cases according to p53 overexpression.

Conclusions: These results suggest that the immunohistochemical detection of p53 accumulation is a useful indicator of poor prognosis in the intestinal but not in the diffuse type of gastric cancer, and are indicative of distinct molecular pathways and pattern of progression in the two histotypes.

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REFERENCES

  1. Black RJ, Bray F, Ferlay J, Parkin DM. Cancer incidence and mortality in the European Union: cancer registry data and estimates of national incidence for 1990. Eur J Cancer 1997;33:1075–1107.

    PubMed  CAS  Google Scholar 

  2. Pinto E, Roviello F, De Stefano A, Vindigni C. Early gastric cancer: report on 142 cases observed over 13 years. Jpn J Clin Oncol 1994;24:12–19.

    PubMed  CAS  Google Scholar 

  3. Akoh JA, Macintyre IMC. Improving survival in gastric cancer review of 5-year survival rates in English language publications from 1970. Br J Surg 1992;79:293–299.

    PubMed  CAS  Google Scholar 

  4. Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. Acta Pathol Microbiol Scand 1965;64:31–49.

    CAS  PubMed  Google Scholar 

  5. Lauren P, Nevalainen T. Epidemiology of intestinal and diffuse types of gastric carcinoma: a time-trend study in Finland with comparison between studies from high- and low-risk areas. Cancer 1993;71:2926–2933.

    PubMed  CAS  Google Scholar 

  6. Amorosi A, Bianchi S, Buiatti E, Cipriani F, Palli D, Zampi G. Gastric Cancer in a high-risk area in Italy: histopathologic patterns according to Lauren’s classification. Cancer 1988;62:2191–2196.

    PubMed  CAS  Google Scholar 

  7. Ireland A, Clark GW, DeMeester T. Barrett’s esophagus: the significance of p53 in clinical practice. Ann Surg 1997;225:17–30.

    PubMed  CAS  Google Scholar 

  8. Bartek J, Bartkova J, Vojtesek B, et al. Aberrant expression of the p53 oncoprotein is a common feature of a wide spectrum of human malignancies. Oncogene 1991;5:1699–1703.

    Google Scholar 

  9. Manne U, Myers RB, Moron C, et al. Prognostic significance of Bcl-2 expression and p53 nuclear accumulation in colorectal adenocarcinoma. Int J Cancer 1997;74:346–358.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  11. Thor AD, Moore DH, Edgerton SM, et al. Accumulation of p53 tumour suppressor gene protein: an independent marker of prognosis in breast cancers. J Natl Cancer Inst 1992;84:845–855.

    PubMed  CAS  Google Scholar 

  12. Ishida H, Irie K, Itoh T, Furukawa T, Tokunaga O. The prognostic significance of p53 and bcl-2 expression in lung adenocarcinoma and its correlation with Ki-67 growth fraction. Cancer 1997;80:1034–1045.

    PubMed  CAS  Google Scholar 

  13. Passlick B, Izbicki JR, Haussinger K, Thetter O, Pantel K. Immunohistochemical detection of p53 protein is not associated with a poor prognosis in non-small-cell lung cancer. J Thorac Cardiovasc Surg 1995;109:1205–1211.

    PubMed  CAS  Google Scholar 

  14. Poller DN, Baxter KJ, Sheperd NA. p53, and Rb1 protein expression: are they prognostically useful in colorectal cancer? Br J Cancer 1997;75:87–93.

    PubMed  CAS  Google Scholar 

  15. Martin HM, Filipe MI, Morris RW, Lane DP, Silvestre F. p53 expression and prognosis in gastric carcinoma. Int J Cancer 1992;50:859–862.

    PubMed  CAS  Google Scholar 

  16. Joypaul BV, Hopwood D, Newman EL, et al. The prognostic significance of the accumulation of p53 tumour-suppressor gene protein in gastric adenocarcinoma. Br J Cancer 1994;69:943–946.

    PubMed  CAS  Google Scholar 

  17. Starzynska T, Markiewski M, Domagala W, et al. The clinical significance of p53 accumulation in gastric carcinoma. Cancer 1996;77:2005–2012.

    PubMed  CAS  Google Scholar 

  18. Ichiyoshi Y, Oiwa H, Tomisaki S, et al. Overexpression of p53 is associated with growth pattern and prognosis in advanced gastric cancer. Hepatogastroenterology 1997;44:546–553.

    PubMed  CAS  Google Scholar 

  19. Motojima K, Furui J, Kohara N, Ito T, Kanematsu T. Expression of p53 protein in gastric carcinomas is not independently prognostic. Surgery 1994;116:890–895.

    PubMed  CAS  Google Scholar 

  20. Victorzon M, Nordling S, Haglund C, Lundin J, Roberts PJ. Expression of p53 protein as a prognostic factor in patients with gastric cancer. Eur J Cancer 1996;32:215–220.

    Google Scholar 

  21. Muller W, Borchard F. Prognostic influence of p53 expression in gastric cancer. J Pathol 1996;178:255–258.

    PubMed  CAS  Google Scholar 

  22. Monig SP, Eidt S, Zirbes TK, Stippel D, Baldus SE, Pichlmaier H. p53 expression in gastric cancer: clinicopathological correlation and prognostic significance. Dig Dis Sci 1997;42:2463–2467.

    PubMed  CAS  Google Scholar 

  23. Gabbert HE, Muller W, Schneiders A, Meier S, Hommel G. The relationship of p53 expression to the prognosis of 418 patients with gastric carcinoma. Cancer 1995;76:720–726.

    PubMed  CAS  Google Scholar 

  24. Gomyo Y, Ikeda M, Osaki M, et al. Expression of p21 (waf1/cip1/sdi1), but not p53 protein, is a factor in the survival of patients with advanced gastric carcinoma. Cancer 1997;79:2067–2072.

    PubMed  CAS  Google Scholar 

  25. Wu MS, Shun CT, Wang HP, et al. Genetic alterations in gastric cancer: relation to histological subtypes, tumor stage, and Helicobacter pylori infection. Gastroenterology 1997;112:1457–1465.

    PubMed  CAS  Google Scholar 

  26. Tahara E. Genetic alterations in human gastrointestinal Cancers. Cancer 1995;75:1410–1417.

    PubMed  CAS  Google Scholar 

  27. Hermanek P, Sobin LJ. UICC TNM Classification of Malignant Tumors. 4th ed. and 2nd rev. Berlin: Springer-Verlag, 1992.

    Google Scholar 

  28. Seta T, Imazeki F, Yokosuka O, et al. Expression of p53 and p21waf1/cip1 proteins in gastric and esophageal cancers: comparison with mutations of the p53 gene. Dig Dis Sci 1998;43:279–289.

    PubMed  CAS  Google Scholar 

  29. Ranzani GN, Luinetti O, Padovan LS, et al. p53 gene mutations and protein nuclear accumulation are early events in the intestinal type gastric cancer but late events in diffuse type. Cancer Epidemiol Biomarkers Prev 1995;4:223–231.

    PubMed  CAS  Google Scholar 

  30. Hong SIL, Hong WS, Jang JJ, et al. Alterations of p53 gene in primary gastric cancer tissue. Anticancer Res 1994;14:1251–1255.

    PubMed  CAS  Google Scholar 

  31. Lim BHG, Soong R, Grieu F, Robbins PD, House AK, Iacopetta BJ. p53 accumulation and mutation are prognostic indicators of poor survival in human gastric carcinoma. Int J Cancer 1996;69:200–204.

    PubMed  CAS  Google Scholar 

  32. Baas IO, Mulder JWR, Offerhaus GJA, Vogelstein B, Hamilton SR. An evaluation of six antibodies for immunohistochemistry of mutant p53 gene product in archival colorectal neoplasms. J Pathol 1994;172:5–12.

    PubMed  CAS  Google Scholar 

  33. Craanen ME, Blok P, Dekker W, Offerhaus GJA, Tytgat GNJ. Chronology of p53 protein accumulation in gastric carcinogenesis. Gut 1995;36:848–852.

    PubMed  CAS  Google Scholar 

  34. Uchino S, Noguchi M, Ochiai A, Saito T, Kobayashi M, Hirohashi S. p53 mutation in gastric cancer: a genetic model for carcinogenesis is common to gastric and colorectal cancer. Int J Cancer 1993;54:759–764.

    PubMed  CAS  Google Scholar 

  35. Lee WJ, Shun CT, Hong RL, Wu MS, Chan KJ, Chen KM. Overexpression of p53 predicts shorter survival in diffuse type gastric cancer. Br J Surg 1998;85:1138–1142.

    PubMed  CAS  Google Scholar 

  36. Ikeguchi M, Saito H, Katano K, Tsujitani S, Maeta M, Kaibara N. Expression of p53 and p21 are independent prognostic factors in patients with serosal invasion by gastric carcinoma. Dig Dis Sci 1998;43:964–970.

    PubMed  CAS  Google Scholar 

  37. Fonseca L, Yonemura Y, De Aretxabala X, Yamaguchi A, Miwa K, Miyazaki I. p53 detection as a prognostic factor in early gastric cancer. Oncology 1994;51:485–490.

    Article  PubMed  CAS  Google Scholar 

  38. Buonsanti G, Calistri D, Padovan L, et al. Microsatellite instability in intestinal- and diffuse-type gastric carcinoma. J Pathol 1997;182:167–173.

    PubMed  CAS  Google Scholar 

  39. Vollmers HP, Dammrich J, Hensel F, et al. Differential expression of apoptosis receptors on diffuse and intestinal type stomach carcinoma. Cancer 1997;79:433–440.

    PubMed  CAS  Google Scholar 

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Correspondence to Franco Roviello MD.

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Roviello, F., Marrelli, D., Vindigni, C. et al. p53 Accumulation Is a Prognostic Factor in Intestinal-Type Gastric Carcinoma but Not in the Diffuse Type. Ann Surg Oncol 6, 739–745 (1999). https://doi.org/10.1007/s10434-999-0739-3

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  • DOI: https://doi.org/10.1007/s10434-999-0739-3

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