Thrombospondin-1 expression in patients with pathologic stage T3 prostate cancer undergoing radical prostatectomy: association with p53 alterations, tumor angiogenesis, and tumor progression.
OBJECTIVE
To investigate thrombospondin-1 (TSP) expression in patients with prostate cancer undergoing radical prostatectomy. TSP is a p53-dependent inhibitor of tumor angiogenesis. Previous studies have demonstrated that TSP expression is significantly associated with the microvessel density (MVD) count, p53 expression, and disease-specific and overall survival in patients with invasive bladder cancer undergoing radical cystectomy.


METHODS
Radical prostatectomy specimens from 85 patients with pathologic Stage T3 disease were analyzed for TSP expression, p53 nuclear reactivity, and MVD using antigen-retrieval immunohistochemistry. The median follow-up after surgery was 10.6 years (range 1.8 to 15.4). Disease recurrence was defined as a prostate-specific antigen level of 0.2 ng/mL or greater on two consecutive occasions after surgery. TSP expression was graded as present or absent on the basis of the immunoreactivity in the extracellular matrix by persons unaware of the clinical outcome. Specimens were considered p53 positive (altered) if more than 10% of the tumor cells demonstrated nuclear reactivity. The chi-square test was used to determine whether the associations were significant between the pathologic tumor characteristics and the immunohistochemical findings. The log-rank test was used to determine the associations between the immunohistochemical findings and disease recurrence.


RESULTS
TSP and p53 were graded as positive in 21 (26%) and 16 (19%) tumors, respectively. The median MVD count was 111.5. No significant associations were found among p53 status, TSP expression, and MVD. Seminal vesicle invasion and Gleason pattern 4 or 5 disease were significant predictors of disease recurrence. A trend was noted toward a higher rate of disease recurrence for patients with altered p53 expression (p53 positive) or increased MVD. TSP expression was not associated with disease recurrence.


CONCLUSIONS
We found no significant association between TSP expression and p53 status, MVD count, or outcome after radical prostatectomy for patients with pathologic Stage T3 prostate cancer. Our data suggest that p53 and MVD may be associated with outcome in these patients. Additional studies are needed to identify reliable molecular markers of outcome for patients with this disease.
Grossfeld
Gary D
GD
Department ofUrology, University of California, San Francisco, School of Medicine, San Francisco, California 94115-1711, USA.
Carroll
Peter R
PR
Lindeman
Neil
N
Meng
Maxwell
M
Groshen
Susan
S
Feng
An Chen
AC
Hawes
Debra
D
Cote
Richard J
RJ
D000230:Adenocarcinoma / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D014408:Biomarkers, Tumor / Q000032:analysis*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000175:diagnosis; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D019700:Thrombospondin 1 / Q000032:analysis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D014408:Biomarkers, Tumor; D019700:Thrombospondin 1; D016159:Tumor Suppressor Protein p53; D017430:Prostate-Specific Antigen