Increase in Expression of the Copper Transporter ATP7A during Platinum Drug-Based Treatment Is Associated with Poor Survival in Ovarian Cancer Patients

Goli Samimi, Nissi M. Varki, Sharon Wilczynski, Roohangiz Safaei, David S Alberts, Stephen B. Howell

Research output: Contribution to journalArticle

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Abstract

Purpose: The Cu efflux transporter ATP7A is overexpressed in some cisplatin-resistant ovarian carcinoma cell lines. We examined the expression of ATP7A in the major normal human organs and in several types of human malignancies and sought to determine whether ATP7A expression changed during treatment of ovarian carcinomas with Pt-containing regimens. Experimental Design: ATP7A expression was quantified by immunohistochemical staining using microarrays containing normal and malignant tissues, and standard sections of 54 paired tumor samples obtained from ovarian carcinoma patients before and after at least two cycles of platinum-based therapy. Results: ATP7A was expressed in normal endometrium, prostate, testis, and kidney but was not detected in the other major organs. ATP7A was expressed in some of the most common human malignancies, including prostate (7 of 7), breast (10 of 10), lung (8 of 8), colon (5 of 8), and ovary (6 of 7), as well as in a wide variety of other types of malignancy. ATP7A staining was detected in 28 of 54 ovarian carcinomas before treatment. Patients with increased ATP7A expression after treatment (18 of 54) exhibited poorer actuarial survival (P < 0.0057 by log-rank test). Expression of ATP7A either before or after treatment was not associated with other clinical factors. Conclusions: Although ATP7A is not detectable in most normal tissues it is expressed in a considerable fraction of many common tumor types. Enrichment of the tumor for ATP7A-expressing cells during platinum drug-based treatment of ovarian cancers is associated with poor survival. These findings are in agreement with results of in vitro studies from this laboratory demonstrating that increased expression of ATP7A renders cells resistant to cisplatin and carboplatin.

Original languageEnglish (US)
Pages (from-to)5853-5859
Number of pages7
JournalClinical Cancer Research
Volume9
Issue number16 I
StatePublished - Dec 1 2003

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Platinum
Ovarian Neoplasms
Copper
Survival
Pharmaceutical Preparations
Carcinoma
Neoplasms
Cisplatin
Prostate
Therapeutics
Staining and Labeling
Carboplatin
Endometrium
Testis
Ovary
Colon
Breast
Research Design
Kidney
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Increase in Expression of the Copper Transporter ATP7A during Platinum Drug-Based Treatment Is Associated with Poor Survival in Ovarian Cancer Patients. / Samimi, Goli; Varki, Nissi M.; Wilczynski, Sharon; Safaei, Roohangiz; Alberts, David S; Howell, Stephen B.

In: Clinical Cancer Research, Vol. 9, No. 16 I, 01.12.2003, p. 5853-5859.

Research output: Contribution to journalArticle

Samimi, Goli ; Varki, Nissi M. ; Wilczynski, Sharon ; Safaei, Roohangiz ; Alberts, David S ; Howell, Stephen B. / Increase in Expression of the Copper Transporter ATP7A during Platinum Drug-Based Treatment Is Associated with Poor Survival in Ovarian Cancer Patients. In: Clinical Cancer Research. 2003 ; Vol. 9, No. 16 I. pp. 5853-5859.
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abstract = "Purpose: The Cu efflux transporter ATP7A is overexpressed in some cisplatin-resistant ovarian carcinoma cell lines. We examined the expression of ATP7A in the major normal human organs and in several types of human malignancies and sought to determine whether ATP7A expression changed during treatment of ovarian carcinomas with Pt-containing regimens. Experimental Design: ATP7A expression was quantified by immunohistochemical staining using microarrays containing normal and malignant tissues, and standard sections of 54 paired tumor samples obtained from ovarian carcinoma patients before and after at least two cycles of platinum-based therapy. Results: ATP7A was expressed in normal endometrium, prostate, testis, and kidney but was not detected in the other major organs. ATP7A was expressed in some of the most common human malignancies, including prostate (7 of 7), breast (10 of 10), lung (8 of 8), colon (5 of 8), and ovary (6 of 7), as well as in a wide variety of other types of malignancy. ATP7A staining was detected in 28 of 54 ovarian carcinomas before treatment. Patients with increased ATP7A expression after treatment (18 of 54) exhibited poorer actuarial survival (P < 0.0057 by log-rank test). Expression of ATP7A either before or after treatment was not associated with other clinical factors. Conclusions: Although ATP7A is not detectable in most normal tissues it is expressed in a considerable fraction of many common tumor types. Enrichment of the tumor for ATP7A-expressing cells during platinum drug-based treatment of ovarian cancers is associated with poor survival. These findings are in agreement with results of in vitro studies from this laboratory demonstrating that increased expression of ATP7A renders cells resistant to cisplatin and carboplatin.",
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T1 - Increase in Expression of the Copper Transporter ATP7A during Platinum Drug-Based Treatment Is Associated with Poor Survival in Ovarian Cancer Patients

AU - Samimi, Goli

AU - Varki, Nissi M.

AU - Wilczynski, Sharon

AU - Safaei, Roohangiz

AU - Alberts, David S

AU - Howell, Stephen B.

PY - 2003/12/1

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N2 - Purpose: The Cu efflux transporter ATP7A is overexpressed in some cisplatin-resistant ovarian carcinoma cell lines. We examined the expression of ATP7A in the major normal human organs and in several types of human malignancies and sought to determine whether ATP7A expression changed during treatment of ovarian carcinomas with Pt-containing regimens. Experimental Design: ATP7A expression was quantified by immunohistochemical staining using microarrays containing normal and malignant tissues, and standard sections of 54 paired tumor samples obtained from ovarian carcinoma patients before and after at least two cycles of platinum-based therapy. Results: ATP7A was expressed in normal endometrium, prostate, testis, and kidney but was not detected in the other major organs. ATP7A was expressed in some of the most common human malignancies, including prostate (7 of 7), breast (10 of 10), lung (8 of 8), colon (5 of 8), and ovary (6 of 7), as well as in a wide variety of other types of malignancy. ATP7A staining was detected in 28 of 54 ovarian carcinomas before treatment. Patients with increased ATP7A expression after treatment (18 of 54) exhibited poorer actuarial survival (P < 0.0057 by log-rank test). Expression of ATP7A either before or after treatment was not associated with other clinical factors. Conclusions: Although ATP7A is not detectable in most normal tissues it is expressed in a considerable fraction of many common tumor types. Enrichment of the tumor for ATP7A-expressing cells during platinum drug-based treatment of ovarian cancers is associated with poor survival. These findings are in agreement with results of in vitro studies from this laboratory demonstrating that increased expression of ATP7A renders cells resistant to cisplatin and carboplatin.

AB - Purpose: The Cu efflux transporter ATP7A is overexpressed in some cisplatin-resistant ovarian carcinoma cell lines. We examined the expression of ATP7A in the major normal human organs and in several types of human malignancies and sought to determine whether ATP7A expression changed during treatment of ovarian carcinomas with Pt-containing regimens. Experimental Design: ATP7A expression was quantified by immunohistochemical staining using microarrays containing normal and malignant tissues, and standard sections of 54 paired tumor samples obtained from ovarian carcinoma patients before and after at least two cycles of platinum-based therapy. Results: ATP7A was expressed in normal endometrium, prostate, testis, and kidney but was not detected in the other major organs. ATP7A was expressed in some of the most common human malignancies, including prostate (7 of 7), breast (10 of 10), lung (8 of 8), colon (5 of 8), and ovary (6 of 7), as well as in a wide variety of other types of malignancy. ATP7A staining was detected in 28 of 54 ovarian carcinomas before treatment. Patients with increased ATP7A expression after treatment (18 of 54) exhibited poorer actuarial survival (P < 0.0057 by log-rank test). Expression of ATP7A either before or after treatment was not associated with other clinical factors. Conclusions: Although ATP7A is not detectable in most normal tissues it is expressed in a considerable fraction of many common tumor types. Enrichment of the tumor for ATP7A-expressing cells during platinum drug-based treatment of ovarian cancers is associated with poor survival. These findings are in agreement with results of in vitro studies from this laboratory demonstrating that increased expression of ATP7A renders cells resistant to cisplatin and carboplatin.

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