Large-scale independent validation of the nuclear factor-kappa B p65 prognostic biomarker in prostate cancer

Over the last decade, we and others have uncovered a robust association between the nuclear localisation of nuclear factor-kappa B (NF-κB) p65, prostate cancer (PCa) aggressiveness and biochemical recurrence (BCR). Our goal was to validate these results in a large independent cohort of PCa patients...

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Published in:	European journal of cancer (1990) Vol. 49; no. 10; pp. 2441 - 2448
Main Authors:	Gannon, Philippe O., Lessard, Laurent, Stevens, Louis-Mathieu, Forest, Valérie, Bégin, Louis R., Minner, Sarah, Tennstedt, Pierre, Schlomm, Thorsten, Mes-Masson, Anne-Marie, Saad, Fred
Format:	Journal Article
Language:	English
Published:	Kidlington Elsevier Ltd 01.07.2013 Elsevier
Subjects:	Aged Biochemical recurrence Biological and medical sciences Biological marker Biomarkers, Tumor - analysis Cell Nucleus - metabolism Cohort Studies Disease Progression Disease-Free Survival Hematology, Oncology and Palliative Medicine Humans Immunohistochemistry Immunohistochemistry - statistics & numerical data Male Medical sciences Middle Aged Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Multivariate Analysis Neoplasm Recurrence, Local Nuclear factor-kappa B (NF-κB) Pharmacology. Drug treatments Prognosis Proportional Hazards Models Prostate - metabolism Prostate - pathology Prostate - surgery Prostate-Specific Antigen - analysis Prostatectomy - methods Prostatic Neoplasms - diagnosis Prostatic Neoplasms - metabolism Prostatic Neoplasms - surgery Seminal Vesicles - metabolism Seminal Vesicles - pathology Sensitivity and Specificity Severity of Illness Index Tissue Array Analysis - statistics & numerical data Transcription Factor RelA - analysis Tumors Immunohistochemistry Biological marker Nuclear factor-kappa B (NF-κB) Biochemical recurrence Validation Urinary system disease Prognosis Prostate disease Malignant tumor Anatomic pathology Cancerology Transcription factor NFκB Male genital diseases Prostate cancer Cancer
ISSN:	0959-8049, 1879-0852, 1879-0852
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Abstract	Over the last decade, we and others have uncovered a robust association between the nuclear localisation of nuclear factor-kappa B (NF-κB) p65, prostate cancer (PCa) aggressiveness and biochemical recurrence (BCR). Our goal was to validate these results in a large independent cohort of PCa patients who underwent radical prostatectomy. A set of 1826 fully annotated prostate cancers treated by radical prostatectomy were analysed in a tissue microarray (TMA) format for NF-κB p65 immunohistochemistry-based protein expression. We performed standard Cox proportional hazard regression models for follow-up data, bootstrap procedure for model internal validation, Harrell’s concordance index for model discrimination and graphical assessment of predicted versus actual outcomes for model calibration. We observed a significant association between an increase in the nuclear frequency of NF-κB p65 and Gleason score (P<0.001), overall BCR (P<0.001) and development of metastases (P=0.001). NF-κB was found to be an independent predictor of BCR (P<0.001, Cox regression). However its contribution to the predictive accuracy of a multivariate model, which included preoperative PSA, Gleason score, extraprostatic extension, lymph node invasion, seminal vesicle involvement and surgical margin status, was modest. Our study offers validating results linking NF-κB p65 with disease progression using a large cohort of European men. However, the contribution of NF-κB to a post-surgical predictive model appears modest. Further validating work should focus on evaluating the contribution of NF-κB p65 in pre-treatment models.
AbstractList	Over the last decade, we and others have uncovered a robust association between the nuclear localisation of nuclear factor-kappa B (NF-κB) p65, prostate cancer (PCa) aggressiveness and biochemical recurrence (BCR). Our goal was to validate these results in a large independent cohort of PCa patients who underwent radical prostatectomy. A set of 1826 fully annotated prostate cancers treated by radical prostatectomy were analysed in a tissue microarray (TMA) format for NF-κB p65 immunohistochemistry-based protein expression. We performed standard Cox proportional hazard regression models for follow-up data, bootstrap procedure for model internal validation, Harrell’s concordance index for model discrimination and graphical assessment of predicted versus actual outcomes for model calibration. We observed a significant association between an increase in the nuclear frequency of NF-κB p65 and Gleason score (P<0.001), overall BCR (P<0.001) and development of metastases (P=0.001). NF-κB was found to be an independent predictor of BCR (P<0.001, Cox regression). However its contribution to the predictive accuracy of a multivariate model, which included preoperative PSA, Gleason score, extraprostatic extension, lymph node invasion, seminal vesicle involvement and surgical margin status, was modest. Our study offers validating results linking NF-κB p65 with disease progression using a large cohort of European men. However, the contribution of NF-κB to a post-surgical predictive model appears modest. Further validating work should focus on evaluating the contribution of NF-κB p65 in pre-treatment models. Over the last decade, we and others have uncovered a robust association between the nuclear localisation of nuclear factor-kappa B (NF-κB) p65, prostate cancer (PCa) aggressiveness and biochemical recurrence (BCR). Our goal was to validate these results in a large independent cohort of PCa patients who underwent radical prostatectomy.PURPOSEOver the last decade, we and others have uncovered a robust association between the nuclear localisation of nuclear factor-kappa B (NF-κB) p65, prostate cancer (PCa) aggressiveness and biochemical recurrence (BCR). Our goal was to validate these results in a large independent cohort of PCa patients who underwent radical prostatectomy.A set of 1826 fully annotated prostate cancers treated by radical prostatectomy were analysed in a tissue microarray (TMA) format for NF-κB p65 immunohistochemistry-based protein expression. We performed standard Cox proportional hazard regression models for follow-up data, bootstrap procedure for model internal validation, Harrell's concordance index for model discrimination and graphical assessment of predicted versus actual outcomes for model calibration.EXPERIMENTAL DESIGNA set of 1826 fully annotated prostate cancers treated by radical prostatectomy were analysed in a tissue microarray (TMA) format for NF-κB p65 immunohistochemistry-based protein expression. We performed standard Cox proportional hazard regression models for follow-up data, bootstrap procedure for model internal validation, Harrell's concordance index for model discrimination and graphical assessment of predicted versus actual outcomes for model calibration.We observed a significant association between an increase in the nuclear frequency of NF-κB p65 and Gleason score (P<0.001), overall BCR (P<0.001) and development of metastases (P=0.001). NF-κB was found to be an independent predictor of BCR (P<0.001, Cox regression). However its contribution to the predictive accuracy of a multivariate model, which included preoperative PSA, Gleason score, extraprostatic extension, lymph node invasion, seminal vesicle involvement and surgical margin status, was modest.RESULTSWe observed a significant association between an increase in the nuclear frequency of NF-κB p65 and Gleason score (P<0.001), overall BCR (P<0.001) and development of metastases (P=0.001). NF-κB was found to be an independent predictor of BCR (P<0.001, Cox regression). However its contribution to the predictive accuracy of a multivariate model, which included preoperative PSA, Gleason score, extraprostatic extension, lymph node invasion, seminal vesicle involvement and surgical margin status, was modest.Our study offers validating results linking NF-κB p65 with disease progression using a large cohort of European men. However, the contribution of NF-κB to a post-surgical predictive model appears modest. Further validating work should focus on evaluating the contribution of NF-κB p65 in pre-treatment models.CONCLUSIONSOur study offers validating results linking NF-κB p65 with disease progression using a large cohort of European men. However, the contribution of NF-κB to a post-surgical predictive model appears modest. Further validating work should focus on evaluating the contribution of NF-κB p65 in pre-treatment models. Abstract Purpose Over the last decade, we and others have uncovered a robust association between the nuclear localisation of nuclear factor-kappa B (NF-κB) p65, prostate cancer (PCa) aggressiveness and biochemical recurrence (BCR). Our goal was to validate these results in a large independent cohort of PCa patients who underwent radical prostatectomy. Experimental design A set of 1826 fully annotated prostate cancers treated by radical prostatectomy were analysed in a tissue microarray (TMA) format for NF-κB p65 immunohistochemistry-based protein expression. We performed standard Cox proportional hazard regression models for follow-up data, bootstrap procedure for model internal validation, Harrell’s concordance index for model discrimination and graphical assessment of predicted versus actual outcomes for model calibration. Results We observed a significant association between an increase in the nuclear frequency of NF-κB p65 and Gleason score ( P < 0.001), overall BCR ( P < 0.001) and development of metastases ( P = 0.001). NF-κB was found to be an independent predictor of BCR ( P < 0.001, Cox regression). However its contribution to the predictive accuracy of a multivariate model, which included preoperative PSA, Gleason score, extraprostatic extension, lymph node invasion, seminal vesicle involvement and surgical margin status, was modest. Conclusions Our study offers validating results linking NF-κB p65 with disease progression using a large cohort of European men. However, the contribution of NF-κB to a post-surgical predictive model appears modest. Further validating work should focus on evaluating the contribution of NF-κB p65 in pre-treatment models.
Author	Schlomm, Thorsten Forest, Valérie Minner, Sarah Mes-Masson, Anne-Marie Saad, Fred Lessard, Laurent Stevens, Louis-Mathieu Gannon, Philippe O. Tennstedt, Pierre Bégin, Louis R.
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Keywords	Immunohistochemistry Biological marker Nuclear factor-kappa B (NF-κB) Biochemical recurrence Validation Urinary system disease Prognosis Prostate disease Malignant tumor Anatomic pathology Cancerology Transcription factor NFκB Male genital diseases Prostate cancer Cancer
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Snippet	Over the last decade, we and others have uncovered a robust association between the nuclear localisation of nuclear factor-kappa B (NF-κB) p65, prostate cancer... Abstract Purpose Over the last decade, we and others have uncovered a robust association between the nuclear localisation of nuclear factor-kappa B (NF-κB)...
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SubjectTerms	Aged Biochemical recurrence Biological and medical sciences Biological marker Biomarkers, Tumor - analysis Cell Nucleus - metabolism Cohort Studies Disease Progression Disease-Free Survival Hematology, Oncology and Palliative Medicine Humans Immunohistochemistry Immunohistochemistry - statistics & numerical data Male Medical sciences Middle Aged Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Multivariate Analysis Neoplasm Recurrence, Local Nuclear factor-kappa B (NF-κB) Pharmacology. Drug treatments Prognosis Proportional Hazards Models Prostate - metabolism Prostate - pathology Prostate - surgery Prostate-Specific Antigen - analysis Prostatectomy - methods Prostatic Neoplasms - diagnosis Prostatic Neoplasms - metabolism Prostatic Neoplasms - surgery Seminal Vesicles - metabolism Seminal Vesicles - pathology Sensitivity and Specificity Severity of Illness Index Tissue Array Analysis - statistics & numerical data Transcription Factor RelA - analysis Tumors
Title	Large-scale independent validation of the nuclear factor-kappa B p65 prognostic biomarker in prostate cancer
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