Elsevier

Urology

Volume 60, Issue 6, December 2002, Pages 1113-1117
Urology

Basic science
High expression of the Met receptor in prostate cancer metastasis to bone

https://doi.org/10.1016/S0090-4295(02)01954-4Get rights and content

Abstract

Objectives

Expression of the active Met receptor tyrosine kinase causes tumor metastasis in animal models. To begin to analyze whether Met expression might be related to the spread of prostate cancer cells, we investigated whether its expression correlates with prostate-specific antigen recurrence and whether its expression depends on the site of metastasis.

Methods

Ninety radical prostatectomy specimens with a Gleason sum of 6 or 7 and 86 specimens of bone, lymph node, and soft-tissue metastasis were immunohistochemically stained for Met, and a semiquantitative scoring system for Met in heterogeneously positive prostate cancers was applied. Met protein in prostate cancer cell lines was measured by Western blotting.

Results

With the exception of two lymph node metastases, all metastases and 51% of the primary prostate cancers expressed Met. Moreover, the bone metastases expressed significantly more Met than did the lymph node metastases. However, in prostate cancer with a Gleason sum of 6 or 7, Met was not a prognostic marker for prostate-specific antigen recurrence. In prostate cancer cell lines, Met expression correlated inversely with expression of the androgen receptor.

Conclusions

The high expression of the Met receptor tyrosine kinase in bone metastasis renders Met a promising target for nuclear imaging and treatment of metastatic prostate cancer.

Section snippets

Patients

All men underwent radical prostatectomy at the New York Presbyterian Hospital. The operating urologist followed up patients with physical examinations and yearly PSA measurements. Patients without recurrence had a minimum of 5 years of follow-up. No patient received neoadjuvant hormonal therapy or postoperative therapy before the study endpoint, which was a documented biochemical recurrence. The recurrence was defined as two consecutive serum PSA values greater than 0.2 ng/mL. Approval from the

Met expression in normal prostate epithelium

Our data confirm the previous reports that Met is highly expressed in prostate basal cells and in atrophic prostate epithelial cells. The secretory cells were negative by immunohistochemistry for Met membrane expression. The urothelial cells expressed high levels of Met (Fig. 1A). At the transition from urothelium to prostate epithelium, Met staining became confined to the basal cell layer of the prostatic ducts.

Met expression in locally invasive prostate cancer

Met expression was analyzed in a cohort of 90 patients who underwent radical

Comment

The question of whether Met expression correlates with progression to metastatic disease in prostate cancer has not been previously examined. We assembled a cohort of GS 6 and 7 prostate cancers and used serum PSA measurements as a surrogate marker for the detection of tumor progression/metastasis. In this study, we observed no correlation between Met staining and tumor recurrence, although it is conceivable that a different endpoint (eg, survival) or a cohort of patients with high-grade cancer

Conclusions

The immunohistochemical evidence of Met expression in bone metastasis and bone stromal cells justifies the development of Met-directed imaging and therapeutic agents, because therapeutic strategies that attack the tumor, as well as the bone, are more powerful and promising than those that target the tumor alone.

Acknowledgements

To Brian Hutchinson for immunohistochemical staining and Dr. Peter Schlegel for referring patients with recurrent prostate cancer.

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This study was supported by the SPORE in Prostate Cancer, P50 CA 92629.

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