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 language | English (US) |
|---|---|
| Pages (from-to) | 5853-5859 |
| Number of pages | 7 |
| Journal | Clinical Cancer Research |
| Volume | 9 |
| Issue number | 16 I |
| State | Published - Dec 1 2003 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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 journal › Article
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TY - JOUR
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
Y1 - 2003/12/1
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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M3 - Article
C2 - 14676106
AN - SCOPUS:0347447284
VL - 9
SP - 5853
EP - 5859
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 16 I
ER -