Drug resistance in ovarian cancer - the role of p53

R Petty, A Evans, I Duncan, C Kurbacher, I Cree, Russell David Petty

Research output: Contribution to journalArticle

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Abstract

The aims were to determine the importance of p53 and bcl-2 expression on the response to chemotherapy with alkylating agents in patients with ovarian cancer. We have followed the response to chemotherapy in a series of 59 patients with ovarian adenocarcinoma designated as p53 and bcl-2 positive or negative by immunocytochemistry. Of these cases, 50 received either cisplatin + treosulfan or treosulfan alone. Immunocytochemistry for p53 was positive in 28/59 tumors. Patients were grouped according to their response to chemotherapy (stable or progressive disease) assessed at 6, 12, and 18 months. There was increasing divergence of p53+ and p53- tumors over time. Of those which were p53+, 25% showed progression at 6 months, 80% at 12 months and 89% progression at 18 months. In contrast, 23%, 50%, and 67% of p53- tumors showed progression at 6, 12 and 18 months respectively. For bcl-2, in 23/55 positive tumors there was progression in 35%, 78% and 94% compared with 25%, 57% and 59% in bcl-2 negative tumors at 6,12 and 18 months respectively. Those tumors which were bcl-2 and p53 negative were most likely to progress, while those which were bcl-2 and p53 positive had the best prognosis. These differences did not translate into increased overall survival with minimum follow-up of 12 months. This data lends support to our suggestion that despite initially increased susceptibility to alkylating agents, enhanced genomic instability due to p53 inactivation may render tumors more likely to develop resistance to chemotherapy over time. This effect may be altered by bcl-2 function, lack of which will lead to a good response to chemotherapy as the tumor's ability to undergo apoptosis will not be compromised.

Original languageEnglish
Pages (from-to)97-102
Number of pages6
JournalPathology Oncology Research
Volume4
Issue number2
Publication statusPublished - 1998

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Drug Resistance
Ovarian Neoplasms
treosulfan
Neoplasms
Drug Therapy
Alkylating Agents
Immunohistochemistry
Genomic Instability
Cisplatin
Adenocarcinoma
Apoptosis
Survival

Keywords

  • Adenocarcinoma
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Alkylating
  • Antineoplastic Combined Chemotherapy Protocols
  • Apoptosis
  • Busulfan
  • Cisplatin
  • Disease-Free Survival
  • Drug Resistance, Multiple
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Ovarian Neoplasms
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2
  • Retrospective Studies
  • Survival Rate
  • Tumor Suppressor Protein p53

Cite this

Petty, R., Evans, A., Duncan, I., Kurbacher, C., Cree, I., & Petty, R. D. (1998). Drug resistance in ovarian cancer - the role of p53. Pathology Oncology Research, 4(2), 97-102.

Drug resistance in ovarian cancer - the role of p53. / Petty, R; Evans, A; Duncan, I; Kurbacher, C; Cree, I; Petty, Russell David.

In: Pathology Oncology Research, Vol. 4, No. 2, 1998, p. 97-102.

Research output: Contribution to journalArticle

Petty, R, Evans, A, Duncan, I, Kurbacher, C, Cree, I & Petty, RD 1998, 'Drug resistance in ovarian cancer - the role of p53' Pathology Oncology Research, vol. 4, no. 2, pp. 97-102.
Petty R, Evans A, Duncan I, Kurbacher C, Cree I, Petty RD. Drug resistance in ovarian cancer - the role of p53. Pathology Oncology Research. 1998;4(2):97-102.
Petty, R ; Evans, A ; Duncan, I ; Kurbacher, C ; Cree, I ; Petty, Russell David. / Drug resistance in ovarian cancer - the role of p53. In: Pathology Oncology Research. 1998 ; Vol. 4, No. 2. pp. 97-102.
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AB - The aims were to determine the importance of p53 and bcl-2 expression on the response to chemotherapy with alkylating agents in patients with ovarian cancer. We have followed the response to chemotherapy in a series of 59 patients with ovarian adenocarcinoma designated as p53 and bcl-2 positive or negative by immunocytochemistry. Of these cases, 50 received either cisplatin + treosulfan or treosulfan alone. Immunocytochemistry for p53 was positive in 28/59 tumors. Patients were grouped according to their response to chemotherapy (stable or progressive disease) assessed at 6, 12, and 18 months. There was increasing divergence of p53+ and p53- tumors over time. Of those which were p53+, 25% showed progression at 6 months, 80% at 12 months and 89% progression at 18 months. In contrast, 23%, 50%, and 67% of p53- tumors showed progression at 6, 12 and 18 months respectively. For bcl-2, in 23/55 positive tumors there was progression in 35%, 78% and 94% compared with 25%, 57% and 59% in bcl-2 negative tumors at 6,12 and 18 months respectively. Those tumors which were bcl-2 and p53 negative were most likely to progress, while those which were bcl-2 and p53 positive had the best prognosis. These differences did not translate into increased overall survival with minimum follow-up of 12 months. This data lends support to our suggestion that despite initially increased susceptibility to alkylating agents, enhanced genomic instability due to p53 inactivation may render tumors more likely to develop resistance to chemotherapy over time. This effect may be altered by bcl-2 function, lack of which will lead to a good response to chemotherapy as the tumor's ability to undergo apoptosis will not be compromised.

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KW - Aged

KW - Aged, 80 and over

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KW - Apoptosis

KW - Busulfan

KW - Cisplatin

KW - Disease-Free Survival

KW - Drug Resistance, Multiple

KW - Female

KW - Humans

KW - Middle Aged

KW - Neoplasm Staging

KW - Ovarian Neoplasms

KW - Prognosis

KW - Proto-Oncogene Proteins c-bcl-2

KW - Retrospective Studies

KW - Survival Rate

KW - Tumor Suppressor Protein p53

M3 - Article

VL - 4

SP - 97

EP - 102

JO - Pathology Oncology Research

JF - Pathology Oncology Research

SN - 1219-4956

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ER -