Expression of insulin-like growth factor-1 receptor in local and metastatic prostate cancer

Ryan, Charles J.; Haqq, Christopher M.; Simko, Jeffrey; Nonaka, Daisuke F.; Chan, June M.; Weinberg, Vivian; Small, Eric J.; Goldfine, Ira D.

doi:10.1016/j.urolonc.2006.07.019

« Previous Next »Urologic Oncology: Seminars and Original Investigations
Volume 25, Issue 2 , Pages 134-140, March 2007

Expression of insulin-like growth factor-1 receptor in local and metastatic prostate cancer☆

Charles J. Ryan, M.D.
- Department of Medicine, UCSF Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94115, USA
- Corresponding author. Tel.: +1-415-353-9279; fax: +1-415-353-7779.
Christopher M. Haqq, M.D., Ph.D.
- Department of Medicine, UCSF Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94115, USA
Jeffrey Simko, M.D., Ph.D.
- Department of Pathology, UCSF Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94115, USA
Daisuke F. Nonaka, Ph.D.
- Department of Medicine, UCSF Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94115, USA
June M. Chan, D.Sci.
- Department of Epidemiology and Biostatistics, UCSF Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94115, USA
Vivian Weinberg, Ph.D.
- Department of Epidemiology and Biostatistics, UCSF Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94115, USA
Eric J. Small, M.D.
- Department of Medicine, UCSF Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94115, USA
Ira D. Goldfine, M.D.
- Department of Medicine, UCSF Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94115, USA

Received 13 January 2006; received in revised form 29 June 2006; accepted 14 July 2006.

Abstract

Purpose

The insulin-like growth factor (IGF)-1 receptor is currently being targeted in clinical trials in prostate cancer. Despite this targeting, there are conflicting data on the presence of this receptor in human tumor samples, largely because of differences in technique.

Materials and Methods

Immunohistochemistry was used to determine the presence of IGF-1 receptor in frozen normal prostate and prostate cancer specimens. Clinical and pathologic parameters were correlated with IGF-1 receptor intensity and frequency of staining. Only 2–3+ staining on a scale of 0–3 was considered positive in this evaluation.

Results

IGF-1 receptor was expressed in normal prostate epithelium in 6 of 6 patients without cancer and in morphologically normal epithelium adjacent to tumor cells in 21 of 22 patients with cancer studied. IGF-1 receptor was present in the prostate tumor epithelium of 28 of 28 primary tumors, 3 of 5 locally recurrent androgen-independent tumors, and in 4 of 5 metastatic lymph nodes. Stromal staining patterns were positive in 2 of 28 specimens near benign epithelium compared to 19 of 30 specimens of stroma surrounding tumor epithelium (P < 0.0001, Fisher exact test). Stroma adjacent to Gleason grade ≥7 tumors showed higher intensity staining than that adjacent to lower grade tumors (P < 0.001). Expression of the closely related insulin receptor did not show expression in either normal or cancer epithelium, or in adjacent stroma.

Conclusions

This study using frozen tissue shows widespread IGF-1 receptor expression in normal prostate, prostate cancers, and metastases. These data support investigations into IGF-1 receptor as a therapeutic target in prostate cancer.

Keywords: Insulin-like growth factor-1 receptor, Insulin-like growth factor 1, Immunohistochemistry, Prostate cancer

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☆ NIH K23 CA115775-01 supported C.J.R. National Cancer Institute Grants, P50 CA89520, R01 CA101042-01 supported C.M.H. and J.S. National Cancer Institute Grants P50 CA89520, R01 CA101042-01, and the Prostate Cancer Foundation supported J.M.C. The John Kerner and Jay Gershow Funds of the Mount Zion Health Fund supported I.D.G.