Alterations of theTP53 gene and TP53 protein expression in epithelial ovarian cancer before and after chemotherapy
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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.
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.
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.
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 wordsovarian cancer chemoresistance mutation TP53 TP53 protein p53
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- 1.Muggia FM. Cisplatin update. Semin Oncol 1991;18:1–4.Google Scholar
- 20.Righetti SC, Della Torre G, Pilotti S, Menard S, Ottone F, Colnaghi MI, Pierotti MA, Lavarino C, Cornarotti M, Oriana S, Bohm S, Bresciani GL, Spatti G, Zunino FA. A comparative study of p53 gene mutations, protein accumulation, and response to cisplatin-based chemotherapy in advanced ovarian carcinoma. Cancer Res 1996;56:689–693.PubMedGoogle Scholar
- 21.Elledge RM, Gray R, Mansour E, Yu Y, Clark GM, Ravdin P, Osborne CK, Gilchrist K, Davidson NE, Robert N. Accumulation of p53 protein as a possible predictor of response to adjuvant combination chemotherapy with cyclophosphamide, methotrexate, fluorouracil, and prednisone for breast cancer. J Natl Cancer Inst 1995;87: 1254–1256.PubMedGoogle Scholar
- 31.Fritsche M, Haessler C, Brandner G. Nuclear accumulation of p53: an indicator of chromatin injury?. J Cancer Res Clin Oncol 1991;117:30 (abstr).Google Scholar