Relationship of serum testosterone level with proliferating cell nuclear antigen and nm23 protein in human prostatic carcinoma tissue.
OBJECTIVE
To elucidate the biological significance of proliferating cell nuclear antigen (PCNA) and nm23 immunoreactivity in prostatic carcinoma (PC) tissue, both expressions were immunohistochemically analyzed, and the results were compared with the change of the serum testosterone (T) level.


METHODS
The paraffin-embedded materials obtained from 49 untreated PC and 16 hormonally refractory PC (hr-PC) were used. Of the 49 untreated PC, 35 received luteinizing hormone-releasing hormone (LH-RH) analogue treatment, while 14 received a cisplatin-based chemotherapy. The immunohistochemistry of PCNA and nm23 protein was performed using an anti-PCNA monoclonal antibody (PC-10) and an antihuman nm23 polyclonal antibody (OA-11-890), respectively. The serum T level was measured by means of radioimmunoassay.


RESULTS
In both untreated PC and hr-PC, the immunoreactivity of nm23 protein significantly correlated with the PCNA expression. Both PCNA expression and nm23 protein immunoreactivity were higher in poorly differentiated PC than those observed in well-differentiated PC, while no significant difference in the serum T level was observed between poorly and well-differentiated PCs. On the other hand, both PCNA expression and nm23 protein immunoreactivity were significantly higher in hr-PC than those observed in untreated PC, whereas the serum T level was significantly lower in hr-PC. In 35 PCs treated with LH-RH analogue, no significant difference in both PCNA expression and nm23 protein immunoreactivity was found between those specimens obtained before and at 3 months after the treatment, while a significant reduction of the serum T level was noted at 3 months after the treatment. Similarly, in 14 PCs treated with a cisplatin-based chemotherapy, the same change of PCNA expression and nm23 protein immunoreactivity as observed in LH-RH analogue treatment was found, while no significant difference of the serum T level was found.


CONCLUSIONS
These findings appear to indicate that (1) nm23 protein immunoreactivity is interrelated with cellular proliferation in PC tissue and (2) alteration of the serum T level during a short period was not enough to explain the essential change of cellular proliferation of PC tissue, but might reflect other aspects of tumor growth such as apoptosis.
Shiina
H
H
Department of Urology, Shimane Medical University, Izumo, Japan.
Igawa
M
M
Shigeno
K
K
Wada
Y
Y
Yoneda
T
T
Yagi
H
H
Shirakawa
R
R
Nagasaki
M
M
D000951:Antigens, Neoplasm / Q000378:metabolism*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018450:Disease Progression; D004961:Estramustine / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009367:Neoplasm Staging; D009701:Nucleoside-Diphosphate Kinase; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013739:Testosterone / Q000097:blood*; D014157:Transcription Factors / Q000378:metabolism*
D000951:Antigens, Neoplasm; D018906:Antineoplastic Agents, Alkylating; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D054778:NM23 Nucleoside Diphosphate Kinases; D018809:Proliferating Cell Nuclear Antigen; D014157:Transcription Factors; D004961:Estramustine; D013739:Testosterone; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins