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Published in: World Journal of Surgery 6/2017

01-06-2017 | Original Scientific Report

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

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

Published in: World Journal of Surgery | Issue 6/2017

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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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Literature
2.
go back to reference Harris CC, Hollstein M (1993) Clinical implications of the p53 tumor-suppressor gene. N Engl J Med 329:1318–1327CrossRefPubMed Harris CC, Hollstein M (1993) Clinical implications of the p53 tumor-suppressor gene. N Engl J Med 329:1318–1327CrossRefPubMed
3.
go back to reference 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 54:4855–4878PubMed 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 54:4855–4878PubMed
4.
go back to reference 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 17:634–642CrossRefPubMed 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 17:634–642CrossRefPubMed
5.
go back to reference 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 17:804–811CrossRefPubMed 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 17:804–811CrossRefPubMed
6.
go back to reference 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 8:531–539CrossRefPubMedPubMedCentral 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 8:531–539CrossRefPubMedPubMedCentral
7.
go back to reference 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 97:682–689CrossRefPubMed 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 97:682–689CrossRefPubMed
8.
go back to reference 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 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
9.
go back to reference 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 85:791–795CrossRefPubMed 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 85:791–795CrossRefPubMed
10.
go back to reference Shimada H, Nabeya Y, Okazumi S et al (2002) Prognostic significance of serum p53 antibody in patients with esophageal squamous cell carcinoma. Surgery 132:41–47CrossRefPubMed Shimada H, Nabeya Y, Okazumi S et al (2002) Prognostic significance of serum p53 antibody in patients with esophageal squamous cell carcinoma. Surgery 132:41–47CrossRefPubMed
11.
12.
go back to reference 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 14:4082–4086CrossRefPubMedPubMedCentral 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 14:4082–4086CrossRefPubMedPubMedCentral
13.
go back to reference Lowe SW, Ruley HE, Jacks T et al (1993) p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74:957–967CrossRefPubMed Lowe SW, Ruley HE, Jacks T et al (1993) p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74:957–967CrossRefPubMed
15.
go back to reference Lowe SW, Bodis S, McClatchey A et al (1994) p53 status and the efficacy of cancer therapy in vivo. Science 266:807–810CrossRefPubMed Lowe SW, Bodis S, McClatchey A et al (1994) p53 status and the efficacy of cancer therapy in vivo. Science 266:807–810CrossRefPubMed
16.
go back to reference 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 12:251–256PubMed 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 12:251–256PubMed
17.
go back to reference 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 12:128–131CrossRefPubMed 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 12:128–131CrossRefPubMed
18.
go back to reference 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 83:7–18CrossRefPubMed 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 83:7–18CrossRefPubMed
19.
go back to reference Miyashita M, Tajiri T, Sasajima K et al (2003) Response to preoperative chemotherapy affects prognosis in esophageal cancer. Dis Esophagus 16:99–101CrossRefPubMed Miyashita M, Tajiri T, Sasajima K et al (2003) Response to preoperative chemotherapy affects prognosis in esophageal cancer. Dis Esophagus 16:99–101CrossRefPubMed
20.
go back to reference 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 148:908–918CrossRefPubMed 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 148:908–918CrossRefPubMed
Metadata
Title
Peritherapeutic Serum p53 Antibody Titers are Predictors of Survival in Patients with Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemotherapy and Surgery
Authors
Kotaro Yamashita
Tomoki Makino
Koji Tanaka
Makoto Yamasaki
Masaaki Yamamoto
Yasuhiro Miyazaki
Tsuyoshi Takahashi
Yukinori Kurokawa
Kiyokazu Nakajima
Shuji Takiguchi
Masaki Mori
Yuichiro Doki
Publication date
01-06-2017
Publisher
Springer International Publishing
Published in
World Journal of Surgery / Issue 6/2017
Print ISSN: 0364-2313
Electronic ISSN: 1432-2323
DOI
https://doi.org/10.1007/s00268-017-3894-x

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