Altered expression of p27 and Skp2 proteins in prostate cancer of African-American patients

Marija Drobnjak, Jonathan Melamed, Samir Taneja, Kate Melzer, Rosemary Wieczorek, Benjamin Levinson, Anne Zeleniuch-Jacquotte, David Polsky, Jay Ferrara, Roman Perez-Soler, Carlos Cordon-Cardo, Michele Pagano, Iman Osman

Research output: Contribution to journalArticle

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Abstract

Purpose: The purpose is to investigate the clinical relevance of altered patterns of p27 and Skp2 expression in African-American patients with localized prostate cancer. The abundance of p27, an inhibitor of cell proliferation, is controlled by Skp2-dependent proteolysis. Experimental Design: A well-characterized cohort of 162 African-Americans who underwent radical prostatectomy at the Veterans Affairs Medical Center of New York between 1990 and 2000 was studied. We analyzed p27 and Skp2 expression by immunohistochemistry. Altered expression of p27 (defined as <40% tumor cells expressing the protein) and Skp2 (defined as ≥20% tumor cells expressing the protein) were correlated with clinicopathological parameters and time to prostate-specific antigen (PSA) recurrence. Results: Altered expression of p27 and Skp2 was observed in 112 of 162 (69.1%) and 93 of 162 (57.4%) cases, respectively. Inverse patterns of Skp2 and p27 protein expression were seen in 87 of 162 (53.7%) cases. A marginally significant association was found between Skp2 overexpression and extracapsular extension (P = 0.065). Moreover, patients with Skp2 overexpression had a 2.77 years decreased median time to PSA recurrence compared with patients with low Skp2 expression; however, the difference was not statistically significant. In multivariate analysis, only tumor grade and stage independently predicted PSA recurrence in this cohort. Conclusions: Our data suggest a role for Skp2 overexpression in prostate cancer pathogenesis that might not be exclusively related to p27 degradation. More studies are needed to determine the mechanistic role of Skp2 in prostate cancer.

Original languageEnglish (US)
Pages (from-to)2613-2619
Number of pages7
JournalClinical Cancer Research
Volume9
Issue number7
StatePublished - Jul 1 2003
Externally publishedYes

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S-Phase Kinase-Associated Proteins
Prostate-Specific Antigen
African Americans
Prostatic Neoplasms
Recurrence
Neoplasms
Veterans
Prostatectomy
Proteolysis
Research Design
Multivariate Analysis
Immunohistochemistry
Cell Proliferation
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Drobnjak, M., Melamed, J., Taneja, S., Melzer, K., Wieczorek, R., Levinson, B., ... Osman, I. (2003). Altered expression of p27 and Skp2 proteins in prostate cancer of African-American patients. Clinical Cancer Research, 9(7), 2613-2619.

Altered expression of p27 and Skp2 proteins in prostate cancer of African-American patients. / Drobnjak, Marija; Melamed, Jonathan; Taneja, Samir; Melzer, Kate; Wieczorek, Rosemary; Levinson, Benjamin; Zeleniuch-Jacquotte, Anne; Polsky, David; Ferrara, Jay; Perez-Soler, Roman; Cordon-Cardo, Carlos; Pagano, Michele; Osman, Iman.

In: Clinical Cancer Research, Vol. 9, No. 7, 01.07.2003, p. 2613-2619.

Research output: Contribution to journalArticle

Drobnjak, M, Melamed, J, Taneja, S, Melzer, K, Wieczorek, R, Levinson, B, Zeleniuch-Jacquotte, A, Polsky, D, Ferrara, J, Perez-Soler, R, Cordon-Cardo, C, Pagano, M & Osman, I 2003, 'Altered expression of p27 and Skp2 proteins in prostate cancer of African-American patients', Clinical Cancer Research, vol. 9, no. 7, pp. 2613-2619.
Drobnjak M, Melamed J, Taneja S, Melzer K, Wieczorek R, Levinson B et al. Altered expression of p27 and Skp2 proteins in prostate cancer of African-American patients. Clinical Cancer Research. 2003 Jul 1;9(7):2613-2619.
Drobnjak, Marija ; Melamed, Jonathan ; Taneja, Samir ; Melzer, Kate ; Wieczorek, Rosemary ; Levinson, Benjamin ; Zeleniuch-Jacquotte, Anne ; Polsky, David ; Ferrara, Jay ; Perez-Soler, Roman ; Cordon-Cardo, Carlos ; Pagano, Michele ; Osman, Iman. / Altered expression of p27 and Skp2 proteins in prostate cancer of African-American patients. In: Clinical Cancer Research. 2003 ; Vol. 9, No. 7. pp. 2613-2619.
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abstract = "Purpose: The purpose is to investigate the clinical relevance of altered patterns of p27 and Skp2 expression in African-American patients with localized prostate cancer. The abundance of p27, an inhibitor of cell proliferation, is controlled by Skp2-dependent proteolysis. Experimental Design: A well-characterized cohort of 162 African-Americans who underwent radical prostatectomy at the Veterans Affairs Medical Center of New York between 1990 and 2000 was studied. We analyzed p27 and Skp2 expression by immunohistochemistry. Altered expression of p27 (defined as <40{\%} tumor cells expressing the protein) and Skp2 (defined as ≥20{\%} tumor cells expressing the protein) were correlated with clinicopathological parameters and time to prostate-specific antigen (PSA) recurrence. Results: Altered expression of p27 and Skp2 was observed in 112 of 162 (69.1{\%}) and 93 of 162 (57.4{\%}) cases, respectively. Inverse patterns of Skp2 and p27 protein expression were seen in 87 of 162 (53.7{\%}) cases. A marginally significant association was found between Skp2 overexpression and extracapsular extension (P = 0.065). Moreover, patients with Skp2 overexpression had a 2.77 years decreased median time to PSA recurrence compared with patients with low Skp2 expression; however, the difference was not statistically significant. In multivariate analysis, only tumor grade and stage independently predicted PSA recurrence in this cohort. Conclusions: Our data suggest a role for Skp2 overexpression in prostate cancer pathogenesis that might not be exclusively related to p27 degradation. More studies are needed to determine the mechanistic role of Skp2 in prostate cancer.",
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AU - Polsky, David

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N2 - Purpose: The purpose is to investigate the clinical relevance of altered patterns of p27 and Skp2 expression in African-American patients with localized prostate cancer. The abundance of p27, an inhibitor of cell proliferation, is controlled by Skp2-dependent proteolysis. Experimental Design: A well-characterized cohort of 162 African-Americans who underwent radical prostatectomy at the Veterans Affairs Medical Center of New York between 1990 and 2000 was studied. We analyzed p27 and Skp2 expression by immunohistochemistry. Altered expression of p27 (defined as <40% tumor cells expressing the protein) and Skp2 (defined as ≥20% tumor cells expressing the protein) were correlated with clinicopathological parameters and time to prostate-specific antigen (PSA) recurrence. Results: Altered expression of p27 and Skp2 was observed in 112 of 162 (69.1%) and 93 of 162 (57.4%) cases, respectively. Inverse patterns of Skp2 and p27 protein expression were seen in 87 of 162 (53.7%) cases. A marginally significant association was found between Skp2 overexpression and extracapsular extension (P = 0.065). Moreover, patients with Skp2 overexpression had a 2.77 years decreased median time to PSA recurrence compared with patients with low Skp2 expression; however, the difference was not statistically significant. In multivariate analysis, only tumor grade and stage independently predicted PSA recurrence in this cohort. Conclusions: Our data suggest a role for Skp2 overexpression in prostate cancer pathogenesis that might not be exclusively related to p27 degradation. More studies are needed to determine the mechanistic role of Skp2 in prostate cancer.

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