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International Journal of Clinical Oncology

, Volume 3, Issue 4, pp 240–246 | Cite as

Alterations of theTP53 gene and TP53 protein expression in epithelial ovarian cancer before and after chemotherapy

  • Makoto Okada
  • Junzo Kigawa
  • Yukihisa Minagawa
  • Yasunobu Kanamori
  • Hiroaki Itamochi
  • Xiusi Cheng
  • Tetsuro Ohishi
  • Naoki Terakawa
Original Article

Abstract

Background

A role for theTP53 (alias p53) tumor-suppressor gene in chemoresistance has recently been discussed, but little is known about the clinical relevance of theTP53 gene to chemoresistance. To elucidate the relevance ofTP53 status to chemoresistance, we investigated theTP53 gene and TP53 protein expression in tumors from the same patients, before and after chemotherapy.

Methods

Twenty-one patients with ovarian cancer, who had residual disease after primary surgery, were studied. These patients received chemotherapy consisting of cisplatin, doxorubicin, and cyclophosphamide, and then underwent a second surgery. Polymerase chain reaction-single strand conformation polymorphism analysis and cycle sequencing were performed to determineTP53 mutation. TP53 protein was detected by Western blot analysis.

Results

Of the 21 patients studied, 9 responded to chemotherapy. Mutation of theTP53 gene was seen in 7 patients (2 responders and 5 nonresponders) before chemotherapy. After chemotherapy, another mutation of the gene was observed in 5 patients, all of whom were nonresponders. TP53 protein was detected in 10 patients (3 responders and 7 nonresponders) before chemotherapy. After chemotherapy, the expression of TP53 protein increased in these 3 nonresponders, and became positive in 2 other nonresponders.

Conclusions

This study showed for the first time in clinical investigation that alterations toTP53 could develop in association with chemotherapy, and thatTP53 status may relate to the mechanisms of chemoresistance in patients with epithelial ovarian cancer.

Key words

ovarian cancer chemoresistance mutation TP53 TP53 protein p53 

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Copyright information

© JSCO/CLJ 1998

Authors and Affiliations

  • Makoto Okada
    • 1
  • Junzo Kigawa
    • 1
  • Yukihisa Minagawa
    • 1
  • Yasunobu Kanamori
    • 1
  • Hiroaki Itamochi
    • 1
  • Xiusi Cheng
    • 1
  • Tetsuro Ohishi
    • 1
  • Naoki Terakawa
    • 1
  1. 1.Department of Obstetrics and GynecologyTottori University School of MedicineYonagoJapan

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