Elevated serum progastrin-releasing peptide (31-98) in metastatic and androgen-independent prostate cancer patients.
BACKGROUND
Increases in neuroendocrine phenotype and secretory products are closely correlated with tumor progression and androgen independence in prostate cancer. In this study, we explored this correlation using serum progastrin-releasing peptide (ProGRP), a carboxy-terminal region common to three subtypes of precursors for gastrin-releasing peptide (GRP), which is released from the neuroendocrine phenotype to act as a growth factor.


METHODS
In 60 patients with benign prostatic hyperplasia (BPH) and 200 with prostate cancer, serum ProGRP levels were determined with an enzyme-linked immunosorbent assay (ELISA) kit and evaluated in relation to clinical stage, hormonal treatment, and prostate-specific antigen (PSA) values. Fourteen randomly selected patients were entered in the follow-up study. Additionally, expression of ProGRP as determined by immunohistochemical analysis was compared to that of chromogranin-A (CgA) in tissue samples from several subjects.


RESULTS
We found a positive correlation between PSA and ProGRP in patients with untreated prostate cancer; no correlation was found in the treated groups. The increases in the ProGRP value and in the percentage of patients with higher than normal values were significant (P < 0.0001), especially in the androgen-independent group (P < 0.0001). A longitudinal study showed that, in a subset of patients, the ProGRP values tended to increase transiently when the cancer became androgen independent, but remained unchanged or decreased at the androgen-dependent stage. Positive staining for ProGRP occurred in a different distribution in neuroendocrine tissues than that of staining for CgA.


CONCLUSIONS
The clinical results demonstrated the existence of a regulatory mechanism for GRP, which to date had only been observed in cell lines. These findings suggest that GRP is a growth factor potentially upregulated by androgen but that does not rely principally on androgen modulation. The large overlap in levels of ProGRP among the groups limits the use of this value as a monitoring tool. Measurement of ProGRP, however, does have potential as an independent parameter to evaluate androgen-independent progression and to facilitate a new therapeutic strategy that may compensate for current limitations of diagnosis based on PSA alone.
Yashi
Masahiro
M
Department of Urology, Jichi Medical School, Yakushiji 3311-1, Minamikawachi-machi, Kawachi-gun, Tochigi-ken 329 0498, Japan. yashi@jichi.ac.jp
Muraishi
Osamu
O
Kobayashi
Yutaka
Y
Tokue
Akihiko
A
Nanjo
Hiroshi
H
D000328:Adult; D000368:Aged; D000728:Androgens / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D019886:Gastrin-Releasing Peptide / Q000097:blood*; D005755:Gastrins / Q000097:blood*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010446:Peptide Fragments / Q000097:blood*; D010455:Peptides / Q000097:blood*; D010641:Phenotype; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000473:pathology*; D011498:Protein Precursors / Q000097:blood*; D011994:Recombinant Proteins / Q000097:blood*; D015854:Up-Regulation
D000728:Androgens; D014408:Biomarkers, Tumor; D005755:Gastrins; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D011994:Recombinant Proteins; C087079:pro-gastrin-releasing peptide (31-98); D019886:Gastrin-Releasing Peptide; D017430:Prostate-Specific Antigen