Prognostic value of apoptotic markers in squamous cell carcinoma of the urinary bladder

Ramy Youssef, Payal Kapur, Shahrokh F. Shariat, Tyler Arendt, Wareef Kabbani, Ahmed Mosbah, Hassan Abol-Enein, Mohamed Ghoneim, Yair Lotan

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Apoptotic pathways are important in carcinogenesis. Many studies, involving small numbers of patients, have found an association between one or two apoptotic markers and some of the pathological features of squamous cell carcinoma (SCC). This study included a large number of patients who had undergone radical cystectomy (RC) for SCC with long-term follow-up, allowing us to study biomarker alterations and their prognostic role. This is the first study on the prognostic role of a panel of apoptotic-related markers in SCC of the urinary bladder, introducing the novel concept of a prognostic marker score based on the number of altered markers. We found that apoptotic markers can improve prediction of oncological outcomes after RC for SCC and might potentially help in patient selection for adjunct therapies. OBJECTIVE To evaluate the association of cleaved caspase-3 (CC-3), Bax, COX-2, and p53 expression with pathological features and clinical outcomes in patients with squamous cell carcinoma (SCC) of the urinary bladder. METHODS Immunohistochemistry for CC-3, Bax, COX-2, and p53 was performed on tissue microarray sections of radical cystectomy specimens with pure SCC from 1997 to 2003. The relationship between the expression of these markers and pathological features was assessed. A prognostic marker score (PS) was defined as favourable if ≤2 biomarkers were altered and unfavourable if >2 biomarkers were altered and the association of the PS with oncological outcomes was examined. RESULTS The study included 151 patients, of whom 98 were men and 53 were women, with a mean age of 52 years. SCC was associated with schistosomiasis (bilharziasis) in 122 (81%) patients. Pathological stage was T2 in 50%, T3 in 38%, T1 in 6% and T4 in 6% of patients. Tumours were low grade in 53%, lymph node metastasis was found in 30.5% and lymphovascular invasion was found in 16% of patients. Median follow-up was 63.2 months. Advanced stage was associated with COX-2, p53 and CC-3 alterations and high grade was associated with COX-2 alterations (P < 0.05). The total number of altered markers and unfavourable PS were associated with both disease recurrence and bladder cancer-specific mortality in Kaplan-Meier analyses (P < 0.05). Unfavourable PS was an independent predictor of disease recurrence (hazard ratio [HR] 2.694, 95% confidence interval [CI] 1.386-5.235, P= 0. 003) and bladder cancer-specific mortality (HR 2.868, 95% CI 1.209-6.802, P= 0. 017) in multivariable Cox regression analysis. CONCLUSION Markers of apoptosis pathways may play an important role in the prognosis of SCC of the bladder. An increased number of altered markers and an unfavourable PS may identify patients who might benefit from multimodal therapies.

Original languageEnglish (US)
Pages (from-to)961-966
Number of pages6
JournalBJU International
Volume110
Issue number7
DOIs
StatePublished - Oct 2012

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Squamous Cell Carcinoma
Urinary Bladder
Cystectomy
Caspase 3
Biomarkers
Schistosomiasis
Urinary Bladder Neoplasms
Confidence Intervals
Recurrence
Mortality
Kaplan-Meier Estimate
Patient Selection
Carcinogenesis
Lymph Nodes
Immunohistochemistry
Regression Analysis
Apoptosis
Neoplasm Metastasis
Therapeutics
Neoplasms

Keywords

  • apoptosis
  • Bax
  • bladder cancer markers
  • cleaved caspase-3
  • COX-2
  • p53
  • squamous cell carcinoma

ASJC Scopus subject areas

  • Urology

Cite this

Prognostic value of apoptotic markers in squamous cell carcinoma of the urinary bladder. / Youssef, Ramy; Kapur, Payal; Shariat, Shahrokh F.; Arendt, Tyler; Kabbani, Wareef; Mosbah, Ahmed; Abol-Enein, Hassan; Ghoneim, Mohamed; Lotan, Yair.

In: BJU International, Vol. 110, No. 7, 10.2012, p. 961-966.

Research output: Contribution to journalArticle

Youssef, R, Kapur, P, Shariat, SF, Arendt, T, Kabbani, W, Mosbah, A, Abol-Enein, H, Ghoneim, M & Lotan, Y 2012, 'Prognostic value of apoptotic markers in squamous cell carcinoma of the urinary bladder', BJU International, vol. 110, no. 7, pp. 961-966. https://doi.org/10.1111/j.1464-410X.2012.10949.x
Youssef, Ramy ; Kapur, Payal ; Shariat, Shahrokh F. ; Arendt, Tyler ; Kabbani, Wareef ; Mosbah, Ahmed ; Abol-Enein, Hassan ; Ghoneim, Mohamed ; Lotan, Yair. / Prognostic value of apoptotic markers in squamous cell carcinoma of the urinary bladder. In: BJU International. 2012 ; Vol. 110, No. 7. pp. 961-966.
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abstract = "Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Apoptotic pathways are important in carcinogenesis. Many studies, involving small numbers of patients, have found an association between one or two apoptotic markers and some of the pathological features of squamous cell carcinoma (SCC). This study included a large number of patients who had undergone radical cystectomy (RC) for SCC with long-term follow-up, allowing us to study biomarker alterations and their prognostic role. This is the first study on the prognostic role of a panel of apoptotic-related markers in SCC of the urinary bladder, introducing the novel concept of a prognostic marker score based on the number of altered markers. We found that apoptotic markers can improve prediction of oncological outcomes after RC for SCC and might potentially help in patient selection for adjunct therapies. OBJECTIVE To evaluate the association of cleaved caspase-3 (CC-3), Bax, COX-2, and p53 expression with pathological features and clinical outcomes in patients with squamous cell carcinoma (SCC) of the urinary bladder. METHODS Immunohistochemistry for CC-3, Bax, COX-2, and p53 was performed on tissue microarray sections of radical cystectomy specimens with pure SCC from 1997 to 2003. The relationship between the expression of these markers and pathological features was assessed. A prognostic marker score (PS) was defined as favourable if ≤2 biomarkers were altered and unfavourable if >2 biomarkers were altered and the association of the PS with oncological outcomes was examined. RESULTS The study included 151 patients, of whom 98 were men and 53 were women, with a mean age of 52 years. SCC was associated with schistosomiasis (bilharziasis) in 122 (81{\%}) patients. Pathological stage was T2 in 50{\%}, T3 in 38{\%}, T1 in 6{\%} and T4 in 6{\%} of patients. Tumours were low grade in 53{\%}, lymph node metastasis was found in 30.5{\%} and lymphovascular invasion was found in 16{\%} of patients. Median follow-up was 63.2 months. Advanced stage was associated with COX-2, p53 and CC-3 alterations and high grade was associated with COX-2 alterations (P < 0.05). The total number of altered markers and unfavourable PS were associated with both disease recurrence and bladder cancer-specific mortality in Kaplan-Meier analyses (P < 0.05). Unfavourable PS was an independent predictor of disease recurrence (hazard ratio [HR] 2.694, 95{\%} confidence interval [CI] 1.386-5.235, P= 0. 003) and bladder cancer-specific mortality (HR 2.868, 95{\%} CI 1.209-6.802, P= 0. 017) in multivariable Cox regression analysis. CONCLUSION Markers of apoptosis pathways may play an important role in the prognosis of SCC of the bladder. An increased number of altered markers and an unfavourable PS may identify patients who might benefit from multimodal therapies.",
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TY - JOUR

T1 - Prognostic value of apoptotic markers in squamous cell carcinoma of the urinary bladder

AU - Youssef, Ramy

AU - Kapur, Payal

AU - Shariat, Shahrokh F.

AU - Arendt, Tyler

AU - Kabbani, Wareef

AU - Mosbah, Ahmed

AU - Abol-Enein, Hassan

AU - Ghoneim, Mohamed

AU - Lotan, Yair

PY - 2012/10

Y1 - 2012/10

N2 - Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Apoptotic pathways are important in carcinogenesis. Many studies, involving small numbers of patients, have found an association between one or two apoptotic markers and some of the pathological features of squamous cell carcinoma (SCC). This study included a large number of patients who had undergone radical cystectomy (RC) for SCC with long-term follow-up, allowing us to study biomarker alterations and their prognostic role. This is the first study on the prognostic role of a panel of apoptotic-related markers in SCC of the urinary bladder, introducing the novel concept of a prognostic marker score based on the number of altered markers. We found that apoptotic markers can improve prediction of oncological outcomes after RC for SCC and might potentially help in patient selection for adjunct therapies. OBJECTIVE To evaluate the association of cleaved caspase-3 (CC-3), Bax, COX-2, and p53 expression with pathological features and clinical outcomes in patients with squamous cell carcinoma (SCC) of the urinary bladder. METHODS Immunohistochemistry for CC-3, Bax, COX-2, and p53 was performed on tissue microarray sections of radical cystectomy specimens with pure SCC from 1997 to 2003. The relationship between the expression of these markers and pathological features was assessed. A prognostic marker score (PS) was defined as favourable if ≤2 biomarkers were altered and unfavourable if >2 biomarkers were altered and the association of the PS with oncological outcomes was examined. RESULTS The study included 151 patients, of whom 98 were men and 53 were women, with a mean age of 52 years. SCC was associated with schistosomiasis (bilharziasis) in 122 (81%) patients. Pathological stage was T2 in 50%, T3 in 38%, T1 in 6% and T4 in 6% of patients. Tumours were low grade in 53%, lymph node metastasis was found in 30.5% and lymphovascular invasion was found in 16% of patients. Median follow-up was 63.2 months. Advanced stage was associated with COX-2, p53 and CC-3 alterations and high grade was associated with COX-2 alterations (P < 0.05). The total number of altered markers and unfavourable PS were associated with both disease recurrence and bladder cancer-specific mortality in Kaplan-Meier analyses (P < 0.05). Unfavourable PS was an independent predictor of disease recurrence (hazard ratio [HR] 2.694, 95% confidence interval [CI] 1.386-5.235, P= 0. 003) and bladder cancer-specific mortality (HR 2.868, 95% CI 1.209-6.802, P= 0. 017) in multivariable Cox regression analysis. CONCLUSION Markers of apoptosis pathways may play an important role in the prognosis of SCC of the bladder. An increased number of altered markers and an unfavourable PS may identify patients who might benefit from multimodal therapies.

AB - Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Apoptotic pathways are important in carcinogenesis. Many studies, involving small numbers of patients, have found an association between one or two apoptotic markers and some of the pathological features of squamous cell carcinoma (SCC). This study included a large number of patients who had undergone radical cystectomy (RC) for SCC with long-term follow-up, allowing us to study biomarker alterations and their prognostic role. This is the first study on the prognostic role of a panel of apoptotic-related markers in SCC of the urinary bladder, introducing the novel concept of a prognostic marker score based on the number of altered markers. We found that apoptotic markers can improve prediction of oncological outcomes after RC for SCC and might potentially help in patient selection for adjunct therapies. OBJECTIVE To evaluate the association of cleaved caspase-3 (CC-3), Bax, COX-2, and p53 expression with pathological features and clinical outcomes in patients with squamous cell carcinoma (SCC) of the urinary bladder. METHODS Immunohistochemistry for CC-3, Bax, COX-2, and p53 was performed on tissue microarray sections of radical cystectomy specimens with pure SCC from 1997 to 2003. The relationship between the expression of these markers and pathological features was assessed. A prognostic marker score (PS) was defined as favourable if ≤2 biomarkers were altered and unfavourable if >2 biomarkers were altered and the association of the PS with oncological outcomes was examined. RESULTS The study included 151 patients, of whom 98 were men and 53 were women, with a mean age of 52 years. SCC was associated with schistosomiasis (bilharziasis) in 122 (81%) patients. Pathological stage was T2 in 50%, T3 in 38%, T1 in 6% and T4 in 6% of patients. Tumours were low grade in 53%, lymph node metastasis was found in 30.5% and lymphovascular invasion was found in 16% of patients. Median follow-up was 63.2 months. Advanced stage was associated with COX-2, p53 and CC-3 alterations and high grade was associated with COX-2 alterations (P < 0.05). The total number of altered markers and unfavourable PS were associated with both disease recurrence and bladder cancer-specific mortality in Kaplan-Meier analyses (P < 0.05). Unfavourable PS was an independent predictor of disease recurrence (hazard ratio [HR] 2.694, 95% confidence interval [CI] 1.386-5.235, P= 0. 003) and bladder cancer-specific mortality (HR 2.868, 95% CI 1.209-6.802, P= 0. 017) in multivariable Cox regression analysis. CONCLUSION Markers of apoptosis pathways may play an important role in the prognosis of SCC of the bladder. An increased number of altered markers and an unfavourable PS may identify patients who might benefit from multimodal therapies.

KW - apoptosis

KW - Bax

KW - bladder cancer markers

KW - cleaved caspase-3

KW - COX-2

KW - p53

KW - squamous cell carcinoma

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