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


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 >or=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.
Ryan
Charles J
CJ
Department of Medicine, UCSF Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94115, USA. ryanc@medicine.ucsf.edu <ryanc@medicine.ucsf.edu>
Haqq
Christopher M
CM
Simko
Jeffrey
J
Nonaka
Daisuke F
DF
Chan
June M
JM
Weinberg
Vivian
V
Small
Eric J
EJ
Goldfine
Ira D
ID
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008198:Lymph Nodes; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism
D014408:Biomarkers, Tumor; D011944:Receptors, Androgen; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin