P53 Mutation status predicts pathological response to chemoradiotherapy in locally advanced esophageal cancer

Tomoki Makino, Makoto Yamasaki, Hiroshi Miyata, Setsuko Yoshioka, Shuji Takiguchi, Yoshiyuki Fujiwara, Kiyokazu Nakajima, Toshirou Nishida, Masaki Mori, Yuichiro Doki

Research output: Contribution to journalArticle

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Abstract

Background and Objectives: The p53 gene promotes cell-cycle arrest and apoptosis upon DNA damage and is associated with chemo- and radiosensitivity of cancer cells. However, its clinical significance has not been confirmed, especially in squamous cell carcinoma of the esophagus (ESCC). We investigated the correlation between p53 disorders (gene mutation and protein accumulation) and the effects of chemoradiotherapy (CRT). Patients and Methods: Biopsy specimens obtained before CRT (40-60 Gy; low-dose 5-fluorouracil plus cisplatin) from 64 patients with locally advanced (T2-T4) ESCC were examined for p53 gene mutations (MT) of exons 4-9 by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and protein accumulation by immunohistochemistry (IHC). These were correlated with the pathological effects of CRT and cause-specific survival. Results: Pathological complete response (pCR) was observed in 21.9% (14/64) patients, who showed better survival than non-pCR patients (2-year survival 78.6% versus 40.5%, P = 0.007). p53 mutation (MT)+ and p53 IHC+ were observed in 31.3% (20/64) and 65.6% (42/64) patients, respectively, and each was significantly associated with non-pCR (P = 0.004 and 0.042, respectively). Combined evaluation of p53 MT and p53 IHC correlated well with pCR frequency, showing 0% (0/12) for MT+/IHC+, 0% (0/8) for MT+/IHC-, 20% (6/30) for MT-/IHC+ and 57.1% (8/14) for MT-/IHC-. These results indicate that presence of p53 mutations was associated with non-pCR regardless of IHC status, and that p53 immunoreactivity was helpful in predicting non-pCR among p53 mutation-negative patients. Conclusion: Analysis of ESCC biopsy specimens for p53 gene mutation can identify patients who will not achieve pCR by CRT. The results should be confirmed by large cohort prospective studies.

Original languageEnglish
Pages (from-to)804-811
Number of pages8
JournalAnnals of Surgical Oncology
Volume17
Issue number3
DOIs
Publication statusPublished - Mar 1 2010

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Chemoradiotherapy
Esophageal Neoplasms
Mutation
Immunohistochemistry
p53 Genes
Esophagus
Squamous Cell Carcinoma
Survival
Biopsy
Protein Conformation
Radiation Tolerance
Cell Cycle Checkpoints
Fluorouracil
Cisplatin
DNA Damage
Exons
Cohort Studies
Prospective Studies
Apoptosis
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

Makino, T., Yamasaki, M., Miyata, H., Yoshioka, S., Takiguchi, S., Fujiwara, Y., ... Doki, Y. (2010). P53 Mutation status predicts pathological response to chemoradiotherapy in locally advanced esophageal cancer. Annals of Surgical Oncology, 17(3), 804-811. https://doi.org/10.1245/s10434-009-0786-9

P53 Mutation status predicts pathological response to chemoradiotherapy in locally advanced esophageal cancer. / Makino, Tomoki; Yamasaki, Makoto; Miyata, Hiroshi; Yoshioka, Setsuko; Takiguchi, Shuji; Fujiwara, Yoshiyuki; Nakajima, Kiyokazu; Nishida, Toshirou; Mori, Masaki; Doki, Yuichiro.

In: Annals of Surgical Oncology, Vol. 17, No. 3, 01.03.2010, p. 804-811.

Research output: Contribution to journalArticle

Makino, T, Yamasaki, M, Miyata, H, Yoshioka, S, Takiguchi, S, Fujiwara, Y, Nakajima, K, Nishida, T, Mori, M & Doki, Y 2010, 'P53 Mutation status predicts pathological response to chemoradiotherapy in locally advanced esophageal cancer', Annals of Surgical Oncology, vol. 17, no. 3, pp. 804-811. https://doi.org/10.1245/s10434-009-0786-9
Makino, Tomoki ; Yamasaki, Makoto ; Miyata, Hiroshi ; Yoshioka, Setsuko ; Takiguchi, Shuji ; Fujiwara, Yoshiyuki ; Nakajima, Kiyokazu ; Nishida, Toshirou ; Mori, Masaki ; Doki, Yuichiro. / P53 Mutation status predicts pathological response to chemoradiotherapy in locally advanced esophageal cancer. In: Annals of Surgical Oncology. 2010 ; Vol. 17, No. 3. pp. 804-811.
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abstract = "Background and Objectives: The p53 gene promotes cell-cycle arrest and apoptosis upon DNA damage and is associated with chemo- and radiosensitivity of cancer cells. However, its clinical significance has not been confirmed, especially in squamous cell carcinoma of the esophagus (ESCC). We investigated the correlation between p53 disorders (gene mutation and protein accumulation) and the effects of chemoradiotherapy (CRT). Patients and Methods: Biopsy specimens obtained before CRT (40-60 Gy; low-dose 5-fluorouracil plus cisplatin) from 64 patients with locally advanced (T2-T4) ESCC were examined for p53 gene mutations (MT) of exons 4-9 by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and protein accumulation by immunohistochemistry (IHC). These were correlated with the pathological effects of CRT and cause-specific survival. Results: Pathological complete response (pCR) was observed in 21.9{\%} (14/64) patients, who showed better survival than non-pCR patients (2-year survival 78.6{\%} versus 40.5{\%}, P = 0.007). p53 mutation (MT)+ and p53 IHC+ were observed in 31.3{\%} (20/64) and 65.6{\%} (42/64) patients, respectively, and each was significantly associated with non-pCR (P = 0.004 and 0.042, respectively). Combined evaluation of p53 MT and p53 IHC correlated well with pCR frequency, showing 0{\%} (0/12) for MT+/IHC+, 0{\%} (0/8) for MT+/IHC-, 20{\%} (6/30) for MT-/IHC+ and 57.1{\%} (8/14) for MT-/IHC-. These results indicate that presence of p53 mutations was associated with non-pCR regardless of IHC status, and that p53 immunoreactivity was helpful in predicting non-pCR among p53 mutation-negative patients. Conclusion: Analysis of ESCC biopsy specimens for p53 gene mutation can identify patients who will not achieve pCR by CRT. The results should be confirmed by large cohort prospective studies.",
author = "Tomoki Makino and Makoto Yamasaki and Hiroshi Miyata and Setsuko Yoshioka and Shuji Takiguchi and Yoshiyuki Fujiwara and Kiyokazu Nakajima and Toshirou Nishida and Masaki Mori and Yuichiro Doki",
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AU - Makino, Tomoki

AU - Yamasaki, Makoto

AU - Miyata, Hiroshi

AU - Yoshioka, Setsuko

AU - Takiguchi, Shuji

AU - Fujiwara, Yoshiyuki

AU - Nakajima, Kiyokazu

AU - Nishida, Toshirou

AU - Mori, Masaki

AU - Doki, Yuichiro

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N2 - Background and Objectives: The p53 gene promotes cell-cycle arrest and apoptosis upon DNA damage and is associated with chemo- and radiosensitivity of cancer cells. However, its clinical significance has not been confirmed, especially in squamous cell carcinoma of the esophagus (ESCC). We investigated the correlation between p53 disorders (gene mutation and protein accumulation) and the effects of chemoradiotherapy (CRT). Patients and Methods: Biopsy specimens obtained before CRT (40-60 Gy; low-dose 5-fluorouracil plus cisplatin) from 64 patients with locally advanced (T2-T4) ESCC were examined for p53 gene mutations (MT) of exons 4-9 by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and protein accumulation by immunohistochemistry (IHC). These were correlated with the pathological effects of CRT and cause-specific survival. Results: Pathological complete response (pCR) was observed in 21.9% (14/64) patients, who showed better survival than non-pCR patients (2-year survival 78.6% versus 40.5%, P = 0.007). p53 mutation (MT)+ and p53 IHC+ were observed in 31.3% (20/64) and 65.6% (42/64) patients, respectively, and each was significantly associated with non-pCR (P = 0.004 and 0.042, respectively). Combined evaluation of p53 MT and p53 IHC correlated well with pCR frequency, showing 0% (0/12) for MT+/IHC+, 0% (0/8) for MT+/IHC-, 20% (6/30) for MT-/IHC+ and 57.1% (8/14) for MT-/IHC-. These results indicate that presence of p53 mutations was associated with non-pCR regardless of IHC status, and that p53 immunoreactivity was helpful in predicting non-pCR among p53 mutation-negative patients. Conclusion: Analysis of ESCC biopsy specimens for p53 gene mutation can identify patients who will not achieve pCR by CRT. The results should be confirmed by large cohort prospective studies.

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