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Insulin-like growth factor binding proteins IGFBP3, IGFBP4, and IGFBP5 predict endocrine responsiveness in patients with ovarian cancer.
Clin Cancer Res. 2007 Mar 01; 13(5):1438-44.CC

Abstract

PURPOSE

This study sought to explore the predictive value of the insulin-like growth factor (IGF) binding proteins (IGFBP) as markers of response in ovarian cancer patients treated with the aromatase inhibitor letrozole.

EXPERIMENTAL DESIGN

IGFBP mRNA expression in cell lines was measured by quantitative reverse transcription-PCR and IGFBP protein expression measured in sections from primary tumors of patients treated with letrozole by semiquantitative immunohistochemistry.

RESULTS

Quantitative reverse transcription-PCR analysis showed that IGFBP3 and IGFBP5 were down-regulated and IGFBP4 was up-regulated by 17beta-estradiol (E(2)) in an estrogen receptor (ER)-positive ovarian cancer cell line. Expressions of IGFBP1, IGFBP2, and IGFBP6 were unaffected by E(2). The E(2) modulation of these genes was reversed by tamoxifen. Using ERalpha-specific (propyl pyrazole triol) and ERbeta-specific (diarylpropionitrile) agonists, the gene expression modulations produced by E(2) could be replicated by propyl pyrazole triol but not by diarylpropionitrile. For ovarian cancer patients being treated with letrozole, we tested the predictive value of the IGFBPs in paraffin-fixed sections from their primary tumors by semiquantitative immunohistochemistry. Using serum CA125 as an indicator of progression/response, significant differences in expression levels of IGFBPs were observed between tumors from CA125 responding/stable patients compared with tumors from progressing patients. Mean immunoscores for IGFBP3 and IGFBP5 were significantly lower, and mean expression of IGFBP4 was significantly higher in tumors from patients demonstrating CA125 response or stabilization compared with CA125 progression.

CONCLUSION

These results indicate that expression levels of certain IGFBP family members in ovarian cancers are estrogen regulated and can, thus, help identify patients who could benefit from endocrine therapy.

Authors+Show Affiliations

Edinburgh Cancer Research Center, University of Edinburgh, Edinburgh, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17332286

Citation

Walker, Graeme, et al. "Insulin-like Growth Factor Binding Proteins IGFBP3, IGFBP4, and IGFBP5 Predict Endocrine Responsiveness in Patients With Ovarian Cancer." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 13, no. 5, 2007, pp. 1438-44.
Walker G, MacLeod K, Williams AR, et al. Insulin-like growth factor binding proteins IGFBP3, IGFBP4, and IGFBP5 predict endocrine responsiveness in patients with ovarian cancer. Clin Cancer Res. 2007;13(5):1438-44.
Walker, G., MacLeod, K., Williams, A. R., Cameron, D. A., Smyth, J. F., & Langdon, S. P. (2007). Insulin-like growth factor binding proteins IGFBP3, IGFBP4, and IGFBP5 predict endocrine responsiveness in patients with ovarian cancer. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 13(5), 1438-44.
Walker G, et al. Insulin-like Growth Factor Binding Proteins IGFBP3, IGFBP4, and IGFBP5 Predict Endocrine Responsiveness in Patients With Ovarian Cancer. Clin Cancer Res. 2007 Mar 1;13(5):1438-44. PubMed PMID: 17332286.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Insulin-like growth factor binding proteins IGFBP3, IGFBP4, and IGFBP5 predict endocrine responsiveness in patients with ovarian cancer. AU - Walker,Graeme, AU - MacLeod,Kenneth, AU - Williams,Alistair R W, AU - Cameron,David A, AU - Smyth,John F, AU - Langdon,Simon P, PY - 2007/3/3/pubmed PY - 2007/5/10/medline PY - 2007/3/3/entrez SP - 1438 EP - 44 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 13 IS - 5 N2 - PURPOSE: This study sought to explore the predictive value of the insulin-like growth factor (IGF) binding proteins (IGFBP) as markers of response in ovarian cancer patients treated with the aromatase inhibitor letrozole. EXPERIMENTAL DESIGN: IGFBP mRNA expression in cell lines was measured by quantitative reverse transcription-PCR and IGFBP protein expression measured in sections from primary tumors of patients treated with letrozole by semiquantitative immunohistochemistry. RESULTS: Quantitative reverse transcription-PCR analysis showed that IGFBP3 and IGFBP5 were down-regulated and IGFBP4 was up-regulated by 17beta-estradiol (E(2)) in an estrogen receptor (ER)-positive ovarian cancer cell line. Expressions of IGFBP1, IGFBP2, and IGFBP6 were unaffected by E(2). The E(2) modulation of these genes was reversed by tamoxifen. Using ERalpha-specific (propyl pyrazole triol) and ERbeta-specific (diarylpropionitrile) agonists, the gene expression modulations produced by E(2) could be replicated by propyl pyrazole triol but not by diarylpropionitrile. For ovarian cancer patients being treated with letrozole, we tested the predictive value of the IGFBPs in paraffin-fixed sections from their primary tumors by semiquantitative immunohistochemistry. Using serum CA125 as an indicator of progression/response, significant differences in expression levels of IGFBPs were observed between tumors from CA125 responding/stable patients compared with tumors from progressing patients. Mean immunoscores for IGFBP3 and IGFBP5 were significantly lower, and mean expression of IGFBP4 was significantly higher in tumors from patients demonstrating CA125 response or stabilization compared with CA125 progression. CONCLUSION: These results indicate that expression levels of certain IGFBP family members in ovarian cancers are estrogen regulated and can, thus, help identify patients who could benefit from endocrine therapy. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/17332286/Insulin_like_growth_factor_binding_proteins_IGFBP3_IGFBP4_and_IGFBP5_predict_endocrine_responsiveness_in_patients_with_ovarian_cancer_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=17332286 DB - PRIME DP - Unbound Medicine ER -