Human epidermal growth factor receptor 2 expression status provides independent prognostic information in patients with urothelial carcinoma of the urinary bladder

Christian Bolenz, Shahrokh F. Shariat, Pierre I. Karakiewicz, Raheela Ashfaq, Richard Ho, Arthur I Sagalowsky, Yair Lotan

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE: To test whether the expression of human epidermal growth factor receptor 2 (HER-2) is of prognostic value in a contemporary cohort of patients with urothelial carcinoma of the urinary bladder (UCB). PATIENTS AND METHODS: Tissue microarrays of 198 patients were constructed and immunohistochemical stainings were performed on the primary tumours and on lymphatic nodal metastases. All patients were treated with radical cystectomy (RC) and regional lymphadenectomy for UCB. HER-2 expression was assessed using continuous HER-2 expression scores (ranging from 0.1 to 3.9) generated using an automated cellular imaging system. Scores of ≥1.0 in at least 10% of tumour cells were regarded as HER-2 positive. We correlated HER-2 scores with pathological and clinical variables, including disease recurrence and cancer-specific mortality. RESULTS: Of 198 patients undergoing RC with lymphadenectomy, there was HER-2 positivity in 55 primary tumours (27.8%) compared with 44.2% of the evaluable positive lymph nodes (P < 0.001). HER-2 positivity was significantly associated with the presence of lymphovascular invasion (LVI; P = 0.026). With a median (range) follow-up of 35.4 (1.3-176.1) months, 101 patients (51.0%) had UCB recurrence and 82 patients (41.4%) died from the disease. In multivariable analyses that adjusted for the effects of pathological tumour stage, grade, LVI, lymph node metastasis and adjuvant chemotherapy, HER-2 positive patients were at increased risk for both UCB recurrence (hazard ratio [HR] 1.955, P = 0.003) and UCB-specific mortality (HR 2.066, P = 0.004) compared with patients with negative HER-2 expression. CONCLUSION: A positive HER-2 status is associated with aggressive UCB and provides independent prognostic information for UCB recurrence and mortality. Assessment of HER-2 status can be used to identify patients at high risk of disease progression who may benefit from adjuvant HER-2-targeted mono- or combined therapy after RC.

Original languageEnglish (US)
Pages (from-to)1216-1222
Number of pages7
JournalBJU International
Volume106
Issue number8
DOIs
StatePublished - Oct 2010

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Urinary Bladder
Carcinoma
Cystectomy
Recurrence
Neoplasms
Lymph Node Excision
Mortality
human ERBB2 protein
Lymph Nodes
Lymphatic Metastasis
Adjuvant Chemotherapy
Disease Progression
Staining and Labeling
Neoplasm Metastasis

Keywords

  • bladder cancer
  • HER-2
  • immunohistochemistry
  • microarray analysis
  • prognosis
  • treatment protocols

ASJC Scopus subject areas

  • Urology

Cite this

Human epidermal growth factor receptor 2 expression status provides independent prognostic information in patients with urothelial carcinoma of the urinary bladder. / Bolenz, Christian; Shariat, Shahrokh F.; Karakiewicz, Pierre I.; Ashfaq, Raheela; Ho, Richard; Sagalowsky, Arthur I; Lotan, Yair.

In: BJU International, Vol. 106, No. 8, 10.2010, p. 1216-1222.

Research output: Contribution to journalArticle

Bolenz, Christian ; Shariat, Shahrokh F. ; Karakiewicz, Pierre I. ; Ashfaq, Raheela ; Ho, Richard ; Sagalowsky, Arthur I ; Lotan, Yair. / Human epidermal growth factor receptor 2 expression status provides independent prognostic information in patients with urothelial carcinoma of the urinary bladder. In: BJU International. 2010 ; Vol. 106, No. 8. pp. 1216-1222.
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abstract = "OBJECTIVE: To test whether the expression of human epidermal growth factor receptor 2 (HER-2) is of prognostic value in a contemporary cohort of patients with urothelial carcinoma of the urinary bladder (UCB). PATIENTS AND METHODS: Tissue microarrays of 198 patients were constructed and immunohistochemical stainings were performed on the primary tumours and on lymphatic nodal metastases. All patients were treated with radical cystectomy (RC) and regional lymphadenectomy for UCB. HER-2 expression was assessed using continuous HER-2 expression scores (ranging from 0.1 to 3.9) generated using an automated cellular imaging system. Scores of ≥1.0 in at least 10{\%} of tumour cells were regarded as HER-2 positive. We correlated HER-2 scores with pathological and clinical variables, including disease recurrence and cancer-specific mortality. RESULTS: Of 198 patients undergoing RC with lymphadenectomy, there was HER-2 positivity in 55 primary tumours (27.8{\%}) compared with 44.2{\%} of the evaluable positive lymph nodes (P < 0.001). HER-2 positivity was significantly associated with the presence of lymphovascular invasion (LVI; P = 0.026). With a median (range) follow-up of 35.4 (1.3-176.1) months, 101 patients (51.0{\%}) had UCB recurrence and 82 patients (41.4{\%}) died from the disease. In multivariable analyses that adjusted for the effects of pathological tumour stage, grade, LVI, lymph node metastasis and adjuvant chemotherapy, HER-2 positive patients were at increased risk for both UCB recurrence (hazard ratio [HR] 1.955, P = 0.003) and UCB-specific mortality (HR 2.066, P = 0.004) compared with patients with negative HER-2 expression. CONCLUSION: A positive HER-2 status is associated with aggressive UCB and provides independent prognostic information for UCB recurrence and mortality. Assessment of HER-2 status can be used to identify patients at high risk of disease progression who may benefit from adjuvant HER-2-targeted mono- or combined therapy after RC.",
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AU - Bolenz, Christian

AU - Shariat, Shahrokh F.

AU - Karakiewicz, Pierre I.

AU - Ashfaq, Raheela

AU - Ho, Richard

AU - Sagalowsky, Arthur I

AU - Lotan, Yair

PY - 2010/10

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N2 - OBJECTIVE: To test whether the expression of human epidermal growth factor receptor 2 (HER-2) is of prognostic value in a contemporary cohort of patients with urothelial carcinoma of the urinary bladder (UCB). PATIENTS AND METHODS: Tissue microarrays of 198 patients were constructed and immunohistochemical stainings were performed on the primary tumours and on lymphatic nodal metastases. All patients were treated with radical cystectomy (RC) and regional lymphadenectomy for UCB. HER-2 expression was assessed using continuous HER-2 expression scores (ranging from 0.1 to 3.9) generated using an automated cellular imaging system. Scores of ≥1.0 in at least 10% of tumour cells were regarded as HER-2 positive. We correlated HER-2 scores with pathological and clinical variables, including disease recurrence and cancer-specific mortality. RESULTS: Of 198 patients undergoing RC with lymphadenectomy, there was HER-2 positivity in 55 primary tumours (27.8%) compared with 44.2% of the evaluable positive lymph nodes (P < 0.001). HER-2 positivity was significantly associated with the presence of lymphovascular invasion (LVI; P = 0.026). With a median (range) follow-up of 35.4 (1.3-176.1) months, 101 patients (51.0%) had UCB recurrence and 82 patients (41.4%) died from the disease. In multivariable analyses that adjusted for the effects of pathological tumour stage, grade, LVI, lymph node metastasis and adjuvant chemotherapy, HER-2 positive patients were at increased risk for both UCB recurrence (hazard ratio [HR] 1.955, P = 0.003) and UCB-specific mortality (HR 2.066, P = 0.004) compared with patients with negative HER-2 expression. CONCLUSION: A positive HER-2 status is associated with aggressive UCB and provides independent prognostic information for UCB recurrence and mortality. Assessment of HER-2 status can be used to identify patients at high risk of disease progression who may benefit from adjuvant HER-2-targeted mono- or combined therapy after RC.

AB - OBJECTIVE: To test whether the expression of human epidermal growth factor receptor 2 (HER-2) is of prognostic value in a contemporary cohort of patients with urothelial carcinoma of the urinary bladder (UCB). PATIENTS AND METHODS: Tissue microarrays of 198 patients were constructed and immunohistochemical stainings were performed on the primary tumours and on lymphatic nodal metastases. All patients were treated with radical cystectomy (RC) and regional lymphadenectomy for UCB. HER-2 expression was assessed using continuous HER-2 expression scores (ranging from 0.1 to 3.9) generated using an automated cellular imaging system. Scores of ≥1.0 in at least 10% of tumour cells were regarded as HER-2 positive. We correlated HER-2 scores with pathological and clinical variables, including disease recurrence and cancer-specific mortality. RESULTS: Of 198 patients undergoing RC with lymphadenectomy, there was HER-2 positivity in 55 primary tumours (27.8%) compared with 44.2% of the evaluable positive lymph nodes (P < 0.001). HER-2 positivity was significantly associated with the presence of lymphovascular invasion (LVI; P = 0.026). With a median (range) follow-up of 35.4 (1.3-176.1) months, 101 patients (51.0%) had UCB recurrence and 82 patients (41.4%) died from the disease. In multivariable analyses that adjusted for the effects of pathological tumour stage, grade, LVI, lymph node metastasis and adjuvant chemotherapy, HER-2 positive patients were at increased risk for both UCB recurrence (hazard ratio [HR] 1.955, P = 0.003) and UCB-specific mortality (HR 2.066, P = 0.004) compared with patients with negative HER-2 expression. CONCLUSION: A positive HER-2 status is associated with aggressive UCB and provides independent prognostic information for UCB recurrence and mortality. Assessment of HER-2 status can be used to identify patients at high risk of disease progression who may benefit from adjuvant HER-2-targeted mono- or combined therapy after RC.

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