Granin-A, parathyroid hormone-related protein, and calcitonin gene products in neuroendocrine prostate cancer.

Abstract

Background: The importance of the expression of granin A (GRN-A, chromogranin-A), calcitonin (CT) gene products (CGPs), and parathyroid hormone-related protein (PTHrP) has become appreciated in the neuroendocrine (NE) differentiation of prostate cancer. We have studied the prostate expression of these three NE cell products with in vivo and in vitro methods.

Methods: GRN-A secretion was measured by immunoassay in serum samples from patients with prostate cancer. Immunohistology procedures were used to assess GRN-A, CGPs, and PTHrP expression in paraffin-embedded prostate tissue samples. Serum and tumor findings were evaluated according to the patient's clinical status. All three substances were also studied in prostate cancer cell cultures.

Results: GRN-A, PTHrP, and CGPs were all secreted products of prostate cancer. Our studies demonstrated that GRN-A can serve as a prostate cancer serum and tumor marker with clinical value for both diagnosis and prognosis. Elevated serum GRN-A levels identified patients with prostate cancer, including some who did not have elevated serum prostate-specific antigen (PSA) levels. Serum GRN-A concentrations also had prognostic value for prostate cancer. PTHrP and CGPs were expressed in prostate cancer in addition to GRN-A, and all three were secreted by prostate cells in culture. Each had effects on prostate cell growth.

Conclusions: GRN-A, PTHrP, and CGPs are produced and secreted by prostate cells. These three NE cell products can serve as tumor and markers for prostate cancer that have diagnostic and prognostic value. In addition, their derived peptides regulate prostate cell growth. However, studies more conclusive than the preliminary observations of our group and of other investigators are needed to define the roles of PTHrP, GRN-A, and CGPs in prostate cancer.