Alpha1B adrenoceptor expression is a marker of reduced survival and increased tumor recurrence in patients with endometrioid ovarian cancer  

作　　者：Dascha Deutsch Suha Deen Frank Entschladen Clare Coveney Robert Rees Kurt S Zanker Desmond George Powe 

机构地区：[1]Institute of Immunology,University of Witten/Herdecke [2]Department of Cellular Pathology,Queens Medical Centre,Nottingham University Hospitals Trust [3]the John van Geest Cancer Research Centre,Nottingham Trent University

出　　处：《World Journal of Obstetrics and Gynecology》2016年第1期118-126,共9页世界妇产科杂志

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)

摘　　要：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.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 a1B, a2C and b2 adrenoceptor were assessed in unselected ovarian cancer using immunohistochemistry on micro-arrayed archival tissue samples. A database containing clinical and pathology parameters and follow-up was used to investigate the association between adrenoceptor isoform expression with ovarian specific survival and tumor recurrence, using univariate and multivariate statistical analysis. RESULTS： Expression of a1B 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 sub-analysis the expression of a1B in endometrioid cancers （ χ^2 = 5.867, P = 0.015） was found to predict reduced ovarian specifc survival and increased tumor recurrence independently of tumor grade, clinical stage and chemotherapy. An association with clinical outcome was not seen for a2C or b2 AR.CONCLUSION： Alpha1B 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 a1B 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.

关 键 词：Alpha adrenoceptor Beta adrenoceptor b-blockers a-blockers Ovarian cancer Prognosis Cancer therapy 

分 类 号：R605.974[医药卫生—急诊医学] R737.31[医药卫生—外科学]