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Serum p53 antibody as a potential tumor marker in extrahepatic cholangiocarcinoma

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Abstract

Purpose

Only a few studies have evaluated the clinicopathological significance of the p53 protein expression and s-p53-Abs level in patients with cholangiocarcinoma. We therefore analyzed the clinicopathological and prognostic significance of s-p53-Abs in patients with extrahepatic cholangiocarcinoma.

Methods

We prospectively evaluated s-p53-Abs levels before and after surgery in 61 patients with extrahepatic cholangiocarcinoma to determine the relationship between clinicopathological factors and the prognostic significance of s-p53-Abs.

Results

Among a total of 61 primary extrahepatic cholangiocarcinoma cases, 23% were positive for s-p53-Abs. Combination of s-p53-Abs with the conventional serum markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) significantly increased the rate of positive extrahepatic cholangiocarcinoma cases (57% for CEA and/or CA19-9 vs. 75% for CEA and/or CA19-9 and/or s-p53-Abs, P = 0.035). There were no significant differences in clinicopathological factors between the p53-seropositive and p53-seronegative patients. An immunohistochemical analysis showed the presence of significant associations between the intensity (P = 0.003) and extent (P = 0.001) of p53 immunoreactivity and p53-seropositivitly. Although s-p53-Abs was not a significant prognostic factor for the survival in either univariate or multivariate analyses, p53 immunoreactivity was independently associated with a poor survival. Among patients positive for s-p53-Abs before surgery, the s-p53-Abs levels were reduced after surgery in most.

Conclusion

These findings suggested that s-p53-Abs might be associated with p53 immunoreactivity. In addition, s-p53-Abs may be useful for a diagnosis, but was not useful for predicting tumor recurrence or the survival. This study was registered as UMIN000014530.

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References

  1. Blechacz B, Gores GJ. Cholangiocarcinoma: advances in pathogenesis, diagnosis, and treatment. Hepatology. 2008;48:308–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Silsirivanit A, Sawanyawisuth K, Riggins GJ, Wongkham C. Cancer biomarker discovery for cholangiocarcinoma: the high-throughput approaches. J Hepatobiliary Pancreat Sci. 2014;21:388–96.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Iguchi T, Yamashita N, Aishima S, Kuroda Y, Terashi T, Sugimachi K, et al. A comprehensive analysis of immunohistochemical studies in intrahepatic cholangiocarcinoma using the survival tree model. Oncology. 2009;76:293–300.

    Article  PubMed  Google Scholar 

  4. Tannapfel A, Engeland K, Weinans L, Katalinic A, Hauss J, Mössner J, et al. Expression of p73, a novel protein related to the p53 tumour suppressor p53, and apoptosis in cholangiocellular carcinoma of the liver. Br J Cancer. 1999;80:1069–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Furubo S, Harada K, Shimonishi T, Katayanagi K, Tsui W, Nakanuma Y. Protein expression and genetic alterations of p53 and ras in intrahepatic cholangiocarcinoma. Histopathology. 1999;35:230–40.

    Article  CAS  PubMed  Google Scholar 

  6. Shimada H, Ochiai T, Nomura F, Japan p53 Antibody Research Group. Titration of serum p53 antibodies in 1085 patients with various types of malignant tumors. Cancer. 2003;97:682–9.

    Article  PubMed  Google Scholar 

  7. Sheng W, Dong M, Zhou J, Li X, Liu Q, Dong Q, et al. Cooperation among Numb, MDM2 and p53 in the development and progression of pancreatic cancer. Cell Tissue Res. 2013;54:521–32.

    Article  Google Scholar 

  8. Hammel P, Boissier B, Chaumette MT, Piedbois P, Rotman N, Kouyoumdjian JC, et al. Detection and monitoring of serum p53 antibodies in patients with colorectal cancer. Gut. 1997;40:356–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Shimada H, Shiratori T, Takeda A, Matsushita K, Okazumi S, Akutsu Y, et al. Perioperative changes of serum p53 antibody titer is a predictor for survival in patients with esophageal squamous cell carcinoma. World J Surg. 2009;33:272–7.

    Article  PubMed  Google Scholar 

  10. Shimada H, Nabeya Y, Okazumi S, Matsubara H, Funami Y, Shiratori T, et al. Prognostic significance of serum p53 antibody in patients with esophageal squamous cell carcinoma. Surgery. 2002;132:41–7.

    Article  PubMed  Google Scholar 

  11. Houbiers JG, van der Burg SH, van de Watering LM, Tollenaar RA, Brand A, van de Velde CJ, et al. Antibodies against p53 are associated with poor prognosis of colorectal cancer. Br J Cancer. 1995;72:637–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Peyrat JP, Bonneterre J, Lubin R, Vanlemmens L, Fournier J, Soussi T. Prognostic significance of circulating P53 antibodies in patients undergoing surgery for locoregional breast cancer. Lancet. 1995;345:621–2.

    Article  CAS  PubMed  Google Scholar 

  13. Tangkijvanich P, Kasemsupatana K, Janchai A, Kullavanijaya P, Theamboonlers A, Poovorawan Y. Prevalence and clinical relevance of serum anti-p53 antibodies in patients with cholangiocarcinoma. Asian Pac J Allergy Immunol. 2000;18:173–6.

    CAS  PubMed  Google Scholar 

  14. Limpaiboon T, Sripa B, Wongkham S, Bhudhisawasdi V, Chau-in S, Teerajetgul Y. Anti-p53 antibodies and p53 protein expression in cholangiocarcinoma. Hepatogastroenterology. 2004;51:25–8.

    CAS  PubMed  Google Scholar 

  15. Sobin LH, Gospodarowicz MK, Wittekind CH. UICC International Union Against Cancer TNM classification of malignant tumors. 7th ed. New York.

  16. Yoon YI, Hwang S, Lee YJ, Kim KH, Ahn CS, Moon DB, et al. Postresection outcomes of combined hepatocellular carcinoma-cholangiocarcinoma, hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Gastrointest Surg. 2015;20:411–20.

    Article  PubMed  Google Scholar 

  17. Shimada H, Kitabayashi H, Nabeya Y, Okazumi S, Matsubara H, Funami Y, et al. Treatment response and prognosis of patients after recurrence of esophageal cancer. Surgery. 2003;133:24–31.

    Article  PubMed  Google Scholar 

  18. Hsu SM, Raine L, Fanger AH. A comparative study of the peroxidase method and an avidine-biotin complex method for studying polypeptide hormones with radioimmunoassay anti-body. Am J Clin Pathol. 1981;75:734–8.

    Article  CAS  PubMed  Google Scholar 

  19. Ribeiro U Jr, Finkelstein SD, Safatle-Ribeiro AV, Landreneau RJ, Clarke MR, Bakker A, et al. p53 sequence analysis predicts treatment response and outcome of patients with esophageal carcinoma. Cancer. 1998;83:7–18.

    Article  CAS  PubMed  Google Scholar 

  20. Yamasawa K, Nio Y, Dong M, Yamaguchi K, Itakura M. Clinicopathological significance of abnormalities in Gadd45 expression and its relationship to p53 in human pancreatic cancer. Clin Cancer Res. 2002;8:2563–9.

    CAS  PubMed  Google Scholar 

  21. Nathan H, Pawlik TM, Wolfgang CL, Choti MA, Cameron JL, Schulick RD. Trends in survival after surgery for cholangiocarcinoma: a 30-year population-based SEER database analysis. J Gastrointest Surg. 2007;11:1488–96.

    Article  PubMed  Google Scholar 

  22. Chong DQ, Zhu AX. The landscape of targeted therapies for cholangiocarcinoma: current status and emerging targets. Oncotarget. 2016;18:1–18.

    Google Scholar 

  23. Müller M, Meyer M, Schilling T, Ulsperger E, Lehnert T, Zentgraf H, et al. Testing for anti-p53 antibodies increases the diagnostic sensitivity of conventional tumor markers. Int J Oncol. 2006;29:973–80.

    PubMed  Google Scholar 

  24. Shimada H, Takeda A, Arima M, Okazumi S, Matsubara H, Nabeya Y, et al. Serum p53 antibody is a useful tumor marker in superficial esophageal squamous cell carcinoma. Cancer. 2000;15:1677–83.

    Article  Google Scholar 

  25. Ralhan R, Arora S, Chattopadhyay TK, Shukla NK, Mathur M. Circulating p53 antibodies, p53 gene mutational profile and product accumulation in esophageal squamous-cell carcinoma in India. Int J Cancer. 2000;85:791–5.

    Article  CAS  PubMed  Google Scholar 

  26. Wellner UF, Shen Y, Keck T, Jin W, Xu Z. The survival outcome and prognostic factors for distal cholangiocarcinoma following surgical resection: a meta-analysis for the 5-year survival. Surg Today. 2017;47:271–9.

    Article  CAS  PubMed  Google Scholar 

  27. Mattioni M, Soddu S, Prodosmo A, Visca P, Conti S, Alessandrini G, et al. Prognostic role of serum p53 antibodies in lung cancer. BMC Cancer. 2015;15:148.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kressner U, Glimelius B, Bergström R, Påhlman L, Larsson A, Lindmark G. Increased serum p53 antibody levels indicate poor prognosis in patients with colorectal cancer. Br J Cancer. 1998;77:1848–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Tokunaga R, Sakamoto Y, Nakagawa S, Yoshida N, Baba H. The utility of tumor marker combination, including serum P53 antibody, in colorectal cancer treatment. Surg Today. 2017;47:636–42.

    Article  CAS  PubMed  Google Scholar 

  30. Kaira K, Sunose Y, Ohshima Y, Ishioka NS, Arakawa K, Ogawa T, et al. Clinical significance of L-type amino acid transporter 1 expression as a prognostic marker and potential of new targeting therapy in biliary tract cancer. BMC Cancer. 2013;134:82.

    Google Scholar 

  31. Kondo N, Murakami Y, Uemura K, Sudo T, Hashimoto Y, Sasaki H, et al. Elevated perioperative serum CA 19-9 levels are independent predictors of poor survival in patients with resectable cholangiocarcinoma. J Surg Oncol. 2014;110:422–9.

    Article  CAS  PubMed  Google Scholar 

  32. Shimada H, Nagata M, Cho A, Takiguchi N, Kainuma O, Soda H, et al. Long-term monitoring of serum p53 antibody after neoadjuvant chemotherapy and surgery for esophageal adenocarcinoma: report of a case. Surg Today. 2014;44:1957–61.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was partially supported by a Grant-in-aid JSPS KAKENHI (grant number 16K10520).

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Correspondence to Hideaki Shimada.

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Conflict of interest

Hideaki Shimada received research Grants and technical lecture fees from Medical and Biological Laboratories Co., Ltd., Nagoya, Japan. The other authors declare that they have no conflicts of interest.

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Okada, R., Shimada, H., Otsuka, Y. et al. Serum p53 antibody as a potential tumor marker in extrahepatic cholangiocarcinoma. Surg Today 47, 1492–1499 (2017). https://doi.org/10.1007/s00595-017-1540-8

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  • DOI: https://doi.org/10.1007/s00595-017-1540-8

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