Thrombospondin-1 expression in patients with pathologic stage T3 prostate cancer undergoing radical prostatectomy

association with p53 alterations, tumor angiogenesis, and tumor progression

Gary D. Grossfeld, Peter R. Carroll, Neil Lindeman, Maxwell Meng, Susan Groshen, An Chen Feng, Debra Hawes, Richard J Cote

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Objectives. 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.

Original languageEnglish
Pages (from-to)97-102
Number of pages6
JournalUrology
Volume59
Issue number1
DOIs
StatePublished - Jan 23 2002
Externally publishedYes

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Thrombospondin 1
Prostatectomy
Prostatic Neoplasms
Microvessels
Neoplasms
Recurrence
Angiogenesis Inhibitors
Seminal Vesicles
Cystectomy
Chi-Square Distribution
Prostate-Specific Antigen
Urinary Bladder Neoplasms
Extracellular Matrix
Immunohistochemistry
Antigens

ASJC Scopus subject areas

  • Urology

Cite this

Thrombospondin-1 expression in patients with pathologic stage T3 prostate cancer undergoing radical prostatectomy : association with p53 alterations, tumor angiogenesis, and tumor progression. / Grossfeld, Gary D.; Carroll, Peter R.; Lindeman, Neil; Meng, Maxwell; Groshen, Susan; Feng, An Chen; Hawes, Debra; Cote, Richard J.

In: Urology, Vol. 59, No. 1, 23.01.2002, p. 97-102.

Research output: Contribution to journalArticle

Grossfeld, Gary D. ; Carroll, Peter R. ; Lindeman, Neil ; Meng, Maxwell ; Groshen, Susan ; Feng, An Chen ; Hawes, Debra ; Cote, Richard J. / Thrombospondin-1 expression in patients with pathologic stage T3 prostate cancer undergoing radical prostatectomy : association with p53 alterations, tumor angiogenesis, and tumor progression. In: Urology. 2002 ; Vol. 59, No. 1. pp. 97-102.
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abstract = "Objectives. 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.",
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T1 - Thrombospondin-1 expression in patients with pathologic stage T3 prostate cancer undergoing radical prostatectomy

T2 - association with p53 alterations, tumor angiogenesis, and tumor progression

AU - Grossfeld, Gary D.

AU - Carroll, Peter R.

AU - Lindeman, Neil

AU - Meng, Maxwell

AU - Groshen, Susan

AU - Feng, An Chen

AU - Hawes, Debra

AU - Cote, Richard J

PY - 2002/1/23

Y1 - 2002/1/23

N2 - Objectives. 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.

AB - Objectives. 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.

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