Serial analysis of resected prostate cancer suggests up‐regulation of type 1 IGF receptor with disease progression

What’s known on the subject? and What does the study add? In a previous study of diagnostic prostate biopsies, we showed that the insulin‐like growth factor (IGF) receptor is up‐regulated in primary prostate cancers. In this study we identified prostate cancer cases in which multiple transurethral resections had been performed, and showed that IGF receptor expression increased or remained high with disease progression. Thus, the IGF receptor is an attractive therapeutic target for patients with advanced prostate cancer.

OBJECTIVE

• ? To compare immunostaining protocols using different antibodies for the type 1 insulin‐like growth factor receptor (IGF‐1R) in channel transurethal resection of the prostate (chTURP) chips, and to investigate how IGF‐1R expression varies with time in serial prostate cancer specimens from individual patients.

METHODS

• ? We studied IGF‐1R expression in 44 prostate cancer specimens from 18 patients who had undergone serial chTURP at least 3 months apart.
• ? Retrospective analysis of the hospital notes was undertaken to obtain clinical information, including age, Gleason score, prostate‐specific antigen (PSA) level, hormone treatment and metastatic disease status at the time of each operation.
• ? After an optimization process using three commercially‐available IGF‐1R antibodies, we used two antibodies for semiquantititve immunostaining of serial chTURP chips.

RESULTS

• ? Santa Cruz antibody sc713 gave positive staining in IGF‐1R null R– cells, and was not used further. Antibodies from Cell Signaling Technology (Beverly, MA, USA) (CS) and NeoMarkers Inc. (Fremont, CA, USA) (NM) did not stain R– cells and, in prostate tissue, showed staining of the glandular epithelium, with negligible stromal staining. All 44 chTURP samples contained identifiable malignant tissue and, of these, 73% and 64% scored moderately or strongly (score 3 or 4) with the CS and NM antibodies respectively.
• ? There was significant correlation of IGF‐1R scores of malignant tissue between the two antibodies (P < 0.001). By contrast, staining of benign glands showed poor correlation between antibodies: CS gave significantly weaker staining than malignant epithelium in the same sections (P < 0.001), whereas NM showed poor discrimination between malignant and benign glands. IGF‐1R staining scores generated by the CS antibody were used to analyze the clinical data.
• ? Most patients (six of seven) with falling IGF‐1R staining scores were responding to androgen deprivation therapy (confirmed by PSA response) between operations. Conversely, in seven of eight patients who had progression to androgen‐independence between procedures, IGF‐1R levels increased or remained high. Finally, seven of 11 patients who developed radiologically confirmed metastases between procedures showed stable or increasing IGF‐1R staining scores.

CONCLUSION

• ? The present study is the first to assess changes in IGF‐1R expression in serial prostate cancer samples. The results obtained indicate that IGF‐1R expression usually remains high throughout the course of histologically‐proven disease progression in serial specimens, suggesting that the IGF‐1R remains a valid treatment target for advanced prostate cancer.