AIM: To investigate the expression patterns of different adrenoceptor isoforms in ovarian cancer and their association with survival and tumor recurrence. METHODS: The protein expression levels of a1 B, a2 C and b2 ad...AIM: To investigate the expression patterns of different adrenoceptor isoforms in ovarian cancer and their association with survival and tumor recurrence. METHODS: The protein expression levels of a1 B, a2 C and b2 adrenoceptor were assessed in unselected ovarian cancer using immunohistochemistry on microarrayed archival tissue samples. A database containing clinical and pathology parameters and follow-up was usedto investigate the association between adrenoceptor isoform expression with ovarian specific survival and tumor recurrence, using univariate and multivariate statistical analysis. RESULTS: Expression of a1 B showed an association with reduced ovarian specific survival(P = 0.05; CI: 1.00-1.49) and increased tumor recurrence(P = 0.021, CI: 1.04-1.69) in the whole patient group. On subanalysis the expression of a1 B in endometrioid cancers(χ2 = 5.867, P = 0.015) was found to predict reduced ovarian specific survival and increased tumor recurrence independently of tumor grade, clinical stage and chemotherapy. An association with clinical outcome was not seen for a2 C or b2 AR.CONCLUSION: Alpha1 B adrenoceptor protein was found to predict increased risk of tumor recurrence and reduced mortality in patients with endometrioid type ovarian cancer and should be investigated as a biomarker for identifying patients at increased risk of disease progression. Furthermore, a adrenergic receptor antagonists with a1 B selectivity should be investigated as a possible adjuvant therapy for treating patients with endometrioid cancer. Proof of principle could be tested in a retrospective population study.展开更多
基金Supported by Financial support from the Fritz Bender Foundation(Munich,to Dascha Deutsch,Frank Entschladen and Kurt S Zanker)from the Nottingham University Hospital Trustees(contributed to the reagent costs)
文摘AIM: To investigate the expression patterns of different adrenoceptor isoforms in ovarian cancer and their association with survival and tumor recurrence. METHODS: The protein expression levels of a1 B, a2 C and b2 adrenoceptor were assessed in unselected ovarian cancer using immunohistochemistry on microarrayed archival tissue samples. A database containing clinical and pathology parameters and follow-up was usedto investigate the association between adrenoceptor isoform expression with ovarian specific survival and tumor recurrence, using univariate and multivariate statistical analysis. RESULTS: Expression of a1 B showed an association with reduced ovarian specific survival(P = 0.05; CI: 1.00-1.49) and increased tumor recurrence(P = 0.021, CI: 1.04-1.69) in the whole patient group. On subanalysis the expression of a1 B in endometrioid cancers(χ2 = 5.867, P = 0.015) was found to predict reduced ovarian specific survival and increased tumor recurrence independently of tumor grade, clinical stage and chemotherapy. An association with clinical outcome was not seen for a2 C or b2 AR.CONCLUSION: Alpha1 B adrenoceptor protein was found to predict increased risk of tumor recurrence and reduced mortality in patients with endometrioid type ovarian cancer and should be investigated as a biomarker for identifying patients at increased risk of disease progression. Furthermore, a adrenergic receptor antagonists with a1 B selectivity should be investigated as a possible adjuvant therapy for treating patients with endometrioid cancer. Proof of principle could be tested in a retrospective population study.
