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Peritherapeutic Serum p53 Antibody Titers are Predictors of Survival in Patients with Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemotherapy and Surgery

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Abstract

Background

Although the preoperative serum level of p53 antibodies (s-p53-Abs) is reported to be a prognostic factor in esophageal squamous cell carcinoma (ESCC) patients, the clinical significance of post-therapeutic s-p53-Abs or the peritherapeutic changes in s-p53-Abs associated with the prognosis or treatment response of ESCC patients undergoing surgery following preoperative chemotherapy remains unclear.

Methods

s-p53-Abs titers were peritherapeutically measured in 136 ESCC patients who underwent surgery following preoperative chemotherapy in our department from 2008 to 2014. Clinicopathological parameters, including the response to chemotherapy and the recurrence-free survival (RFS), were compared between groups classified by the levels of the s-p53-Ab titers and the peritherapeutic changes in the s-p53-Ab titers.

Results

After curative surgery following preoperative chemotherapy, the s-p53-Ab titers increased in 15 patients (11.0%), remained unchanged in 81 patients (59.6%) and decreased in 40 patients (29.4%). The seropositive rate (cutoff value: 0.5 U/ml) of pre- and post-therapeutic s-p53-Abs were 36.0% (49/136) and 35.3% (48/136), respectively. Negative and positive seroconversion of s-p53-Abs was identified in 20.4% (10/49) and 10.3% (9/105) of patients, respectively. Both pre- and post-therapeutic seropositive s-p53-Ab titers significantly correlated with an unfavorable prognosis (p = 0.028, 0.002, respectively). Patients with a peritherapeutic increase in s-p53-Ab titers showed a shorter RFS compared with unchanged/decreased titers. Neither the s-p53-Ab titer at any time point nor its change was associated with the response to chemotherapy.

Conclusions

Both peritherapeutic s-p53-Ab titers and their changes were shown to be prognostic parameters in ESCC patients undergoing preoperative chemotherapy followed by surgery.

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References

  1. Lane DP (1992) Cancer. p53, guardian of the genome. Nature 358:15–16

    Article  CAS  PubMed  Google Scholar 

  2. Harris CC, Hollstein M (1993) Clinical implications of the p53 tumor-suppressor gene. N Engl J Med 329:1318–1327

    Article  CAS  PubMed  Google Scholar 

  3. Greenblatt MS, Bennett WP, Hollstein M et al (1994) Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res 54:4855–4878

    CAS  PubMed  Google Scholar 

  4. Yamasaki M, Miyata H, Fujiwara Y et al (2010) p53 genotype predicts response to chemotherapy in patients with squamous cell carcinoma of the esophagus. Ann Surg Oncol 17:634–642

    Article  PubMed  Google Scholar 

  5. Makino T, Yamasaki M, Miyata H et al (2010) p53 Mutation status predicts pathological response to chemoradiotherapy in locally advanced esophageal cancer. Ann Surg Oncol 17:804–811

    Article  PubMed  Google Scholar 

  6. Finlay CA, Hinds PW, Tan TH et al (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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Shimada H, Ochiai T, Nomura F (2003) Titration of serum p53 antibodies in 1,085 patients with various types of malignant tumors: a multiinstitutional analysis by the Japan p53 Antibody Research Group. Cancer 97:682–689

    Article  PubMed  Google Scholar 

  8. von Brevern MC, Hollstein MC, Cawley HM et al (1996) Circulating anti-p53 antibodies in esophageal cancer patients are found predominantly in individuals with p53 core domain mutations in their tumors. Cancer Res 56:4917–4921

    Google Scholar 

  9. Ralhan R, Arora S, Chattopadhyay TK et al (2000) Circulating p53 antibodies, p53 gene mutational profile and product accumulation in esophageal squamous-cell carcinoma in India. Int J Cancer 85:791–795

    Article  CAS  PubMed  Google Scholar 

  10. Shimada H, Nabeya Y, Okazumi S et al (2002) Prognostic significance of serum p53 antibody in patients with esophageal squamous cell carcinoma. Surgery 132:41–47

    Article  PubMed  Google Scholar 

  11. Shimada H, Shiratori T, Takeda A et al (2009) Perioperative changes of serum p53 antibody titer is a predictor for survival in patients with esophageal squamous cell carcinoma. World J Surg 33:272–277. doi:10.1007/s00268-008-9821-4

    Article  PubMed  Google Scholar 

  12. Cai HY, Wang XH, Tian Y et al (2008) Changes of serum p53 antibodies and clinical significance of radiotherapy for esophageal squamous cell carcinoma. World J Gastroenterol 14:4082–4086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lowe SW, Ruley HE, Jacks T et al (1993) p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74:957–967

    Article  CAS  PubMed  Google Scholar 

  14. Lee JM, Bernstein A (1993) p53 mutations increase resistance to ionizing radiation. Proc Natl Acad Sci USA 90:5742–5746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Lowe SW, Bodis S, McClatchey A et al (1994) p53 status and the efficacy of cancer therapy in vivo. Science 266:807–810

    Article  CAS  PubMed  Google Scholar 

  16. Yang B, Rice TW, Adelstein DJ et al (1999) Overexpression of p53 protein associates decreased response to chemoradiotherapy in patients with esophageal carcinoma. Mod Pathol 12:251–256

    CAS  PubMed  Google Scholar 

  17. Nasierowska-Guttmejer A, Szawlowski A, Jastrzebska M et al (1999) p53 Protein accumulation as a prognostic marker of preoperative radiotherapy and/or chemotherapy in advanced squamous cell esophageal carcinoma—preliminary report. Dis Esophagus 12:128–131

    Article  CAS  PubMed  Google Scholar 

  18. Ribeiro U Jr, Finkelstein SD, Safatle-Ribeiro AV et al (1998) p53 sequence analysis predicts treatment response and outcome of patients with esophageal carcinoma. Cancer 83:7–18

    Article  CAS  PubMed  Google Scholar 

  19. Miyashita M, Tajiri T, Sasajima K et al (2003) Response to preoperative chemotherapy affects prognosis in esophageal cancer. Dis Esophagus 16:99–101

    Article  CAS  PubMed  Google Scholar 

  20. Makino T, Miyata H, Yamasaki M et al (2010) Utility of response evaluation to neo-adjuvant chemotherapy by (18)F-fluorodeoxyglucose-positron emission tomography in locally advanced esophageal squamous cell carcinoma. Surgery 148:908–918

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita City, Osaka, 565-0871, Japan

    Kotaro Yamashita, Tomoki Makino, Koji Tanaka, Makoto Yamasaki, Masaaki Yamamoto, Yasuhiro Miyazaki, Tsuyoshi Takahashi, Yukinori Kurokawa, Kiyokazu Nakajima, Shuji Takiguchi, Masaki Mori & Yuichiro Doki

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  1. Kotaro Yamashita
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  2. Tomoki Makino
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  3. Koji Tanaka
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  4. Makoto Yamasaki
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  5. Masaaki Yamamoto
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  6. Yasuhiro Miyazaki
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  7. Tsuyoshi Takahashi
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  8. Yukinori Kurokawa
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  9. Kiyokazu Nakajima
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  10. Shuji Takiguchi
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  11. Masaki Mori
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  12. Yuichiro Doki
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Corresponding author

Correspondence to Tomoki Makino.

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Yamashita, K., Makino, T., Tanaka, K. et al. Peritherapeutic Serum p53 Antibody Titers are Predictors of Survival in Patients with Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemotherapy and Surgery. World J Surg 41, 1566–1574 (2017). https://doi.org/10.1007/s00268-017-3894-x

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  • DOI: https://doi.org/10.1007/s00268-017-3894-x

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