Pan-cadherin as a high level phenotypic biomarker for prostate cancer

Nizar K. Wehbi, Ashley L. Dugger, Rebecca B. Bonner, Jan V. Pitha, Robert E. Hurst, George P. Hemstreet

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Purpose: High level phenotypic biomarkers such as cadherins are needed to identify individuals at risk for biologically active prostate cancer and determine which individuals with elevated prostate specific antigen or a prostate nodule are candidates for re-biopsy. Cadherins are a high level phenotypic biomarker associated with decreased cell adhesion, which is a cardinal event in carcinogenesis. Recently we reported that G-actin and tissue transglutaminase type II are potential biomarkers for prostate cancer. In this study we present cadherins as a potential third component of the biomarker profile. Materials and Methods: Prostate tissues from 38 patients with cancer and 33 controls with a 10-year prostate cancer-free followup were labeled for pan-cadherin by immunohistochemical testing. Immunoreactivity was quantified using a Pathology Workstation (Autocyte Inc., Elon College, North Carolina). Results: Visually benign glands from controls generally expressed cadherins, whereas regions of adenocarcinoma were generally negative. On quantitative immunohistochemistry 36 of 38 prostate cancer cases expressed a lower mean percent area positive for cadherin than the 19 benign prostatic hyperplasia and 14 prostatitis cases (odds ratio 978, 95% confidence interval 45 to 21,140, relative risk 18, 95% confidence interval 5 to 67, p <0.0001). Receiver operating characteristics analysis of immunohistochemical testing data showed that an optimal threshold of 7 produced 95% sensitivity and 100% specificity. Conclusions: Quantitative down-regulation of cadherin expression in prostate cancer tissue sections is a strong biomarker for prostate cancer. Analysis of cadherin and other high level phenotypic biomarker expression in the premalignant field may provide additional diagnostic information to decide which patients need re-biopsy, more intensive monitoring or chemoprevention.

Original languageEnglish (US)
Pages (from-to)2215-2221
Number of pages7
JournalJournal of Urology
Volume167
Issue number5
DOIs
StatePublished - Jan 1 2002

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Cadherins
Prostatic Neoplasms
Biomarkers
Prostate
Confidence Intervals
Biopsy
Prostatitis
Chemoprevention
Prostatic Hyperplasia
Prostate-Specific Antigen
Cell Adhesion
ROC Curve
Actins
Carcinogenesis
Adenocarcinoma
Down-Regulation
Immunohistochemistry
Odds Ratio
Pathology
Sensitivity and Specificity

Keywords

  • Adenocarcinoma
  • Cadherins
  • Prostate
  • Prostatic neoplasms
  • Tumor markers, biological

ASJC Scopus subject areas

  • Urology

Cite this

Wehbi, N. K., Dugger, A. L., Bonner, R. B., Pitha, J. V., Hurst, R. E., & Hemstreet, G. P. (2002). Pan-cadherin as a high level phenotypic biomarker for prostate cancer. Journal of Urology, 167(5), 2215-2221. https://doi.org/10.1016/S0022-5347(05)65131-2

Pan-cadherin as a high level phenotypic biomarker for prostate cancer. / Wehbi, Nizar K.; Dugger, Ashley L.; Bonner, Rebecca B.; Pitha, Jan V.; Hurst, Robert E.; Hemstreet, George P.

In: Journal of Urology, Vol. 167, No. 5, 01.01.2002, p. 2215-2221.

Research output: Contribution to journalArticle

Wehbi, NK, Dugger, AL, Bonner, RB, Pitha, JV, Hurst, RE & Hemstreet, GP 2002, 'Pan-cadherin as a high level phenotypic biomarker for prostate cancer', Journal of Urology, vol. 167, no. 5, pp. 2215-2221. https://doi.org/10.1016/S0022-5347(05)65131-2
Wehbi, Nizar K. ; Dugger, Ashley L. ; Bonner, Rebecca B. ; Pitha, Jan V. ; Hurst, Robert E. ; Hemstreet, George P. / Pan-cadherin as a high level phenotypic biomarker for prostate cancer. In: Journal of Urology. 2002 ; Vol. 167, No. 5. pp. 2215-2221.
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N2 - Purpose: High level phenotypic biomarkers such as cadherins are needed to identify individuals at risk for biologically active prostate cancer and determine which individuals with elevated prostate specific antigen or a prostate nodule are candidates for re-biopsy. Cadherins are a high level phenotypic biomarker associated with decreased cell adhesion, which is a cardinal event in carcinogenesis. Recently we reported that G-actin and tissue transglutaminase type II are potential biomarkers for prostate cancer. In this study we present cadherins as a potential third component of the biomarker profile. Materials and Methods: Prostate tissues from 38 patients with cancer and 33 controls with a 10-year prostate cancer-free followup were labeled for pan-cadherin by immunohistochemical testing. Immunoreactivity was quantified using a Pathology Workstation (Autocyte Inc., Elon College, North Carolina). Results: Visually benign glands from controls generally expressed cadherins, whereas regions of adenocarcinoma were generally negative. On quantitative immunohistochemistry 36 of 38 prostate cancer cases expressed a lower mean percent area positive for cadherin than the 19 benign prostatic hyperplasia and 14 prostatitis cases (odds ratio 978, 95% confidence interval 45 to 21,140, relative risk 18, 95% confidence interval 5 to 67, p <0.0001). Receiver operating characteristics analysis of immunohistochemical testing data showed that an optimal threshold of 7 produced 95% sensitivity and 100% specificity. Conclusions: Quantitative down-regulation of cadherin expression in prostate cancer tissue sections is a strong biomarker for prostate cancer. Analysis of cadherin and other high level phenotypic biomarker expression in the premalignant field may provide additional diagnostic information to decide which patients need re-biopsy, more intensive monitoring or chemoprevention.

AB - Purpose: High level phenotypic biomarkers such as cadherins are needed to identify individuals at risk for biologically active prostate cancer and determine which individuals with elevated prostate specific antigen or a prostate nodule are candidates for re-biopsy. Cadherins are a high level phenotypic biomarker associated with decreased cell adhesion, which is a cardinal event in carcinogenesis. Recently we reported that G-actin and tissue transglutaminase type II are potential biomarkers for prostate cancer. In this study we present cadherins as a potential third component of the biomarker profile. Materials and Methods: Prostate tissues from 38 patients with cancer and 33 controls with a 10-year prostate cancer-free followup were labeled for pan-cadherin by immunohistochemical testing. Immunoreactivity was quantified using a Pathology Workstation (Autocyte Inc., Elon College, North Carolina). Results: Visually benign glands from controls generally expressed cadherins, whereas regions of adenocarcinoma were generally negative. On quantitative immunohistochemistry 36 of 38 prostate cancer cases expressed a lower mean percent area positive for cadherin than the 19 benign prostatic hyperplasia and 14 prostatitis cases (odds ratio 978, 95% confidence interval 45 to 21,140, relative risk 18, 95% confidence interval 5 to 67, p <0.0001). Receiver operating characteristics analysis of immunohistochemical testing data showed that an optimal threshold of 7 produced 95% sensitivity and 100% specificity. Conclusions: Quantitative down-regulation of cadherin expression in prostate cancer tissue sections is a strong biomarker for prostate cancer. Analysis of cadherin and other high level phenotypic biomarker expression in the premalignant field may provide additional diagnostic information to decide which patients need re-biopsy, more intensive monitoring or chemoprevention.

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