A clinically applicable molecular classification for high-grade serous ovarian cancer based on hormone receptor expression

被引:43
作者
Feng, Zheng [1 ,2 ]
Wen, Hao [1 ,2 ]
Bi, Rui [2 ,3 ]
Ju, Xingzhu [1 ,2 ]
Chen, Xiaojun [1 ,2 ]
Yang, Wentao [2 ,3 ]
Wu, Xiaohua [1 ,2 ]
机构
[1] Fudan Univ, Shanghai Canc Ctr, Dept Gynecol Oncol, Shanghai 200032, Peoples R China
[2] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China
[3] Fudan Univ, Shanghai Canc Ctr, Dept Pathol, Shanghai 200032, Peoples R China
关键词
INTERNATIONAL EXPERT CONSENSUS; FOLLICLE-STIMULATING-HORMONE; PRIMARY THERAPY; BREAST CANCERS; ESTROGEN; PROGNOSIS; CARCINOMA; ANDROGEN; HIGHLIGHTS; LETROZOLE;
D O I
10.1038/srep25408
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
To establish an effective hormone receptor-based molecular classification of high-grade serous ovarian cancer (HGSC), we retrospectively examined 875 consecutive HGSC patients who underwent primary surgery at our hospital and constructed tissue microarrays from these specimens. The expression levels of the hormone receptors were as follows: ER 64.4%, PR 12.6%, AR 35.6%, FSHR 54.5%, LHR 34.8%, and GnRHR 88.3%. Based on clustering of their expression patterns, we classified patients into five subgroups with distinctive clinical features (PR+, PR - ER + AR+, PR - ER + AR-, PR - ER - AR+, and PR - ER - AR-). Patients in the PR + group were younger compared to those in the other groups (p < 0.001). More patients were of advanced stage in the PR - ER + AR- group than the other groups (p = 0.020). A greater proportion of patients were sensitive to platinum-based chemotherapy in the PR - ER - AR + group compared with the other groups (p = 0.034). A trend of increasing risk of death was observed among these subgroups (p < 0.001). In the multivariate analysis, patients also had orderly increased hazard ratios for death in the PR + (HR = 2.256, 95% CI, 0.983-5.175), PR - ER + AR + (HR = 2.188, 95% CI, 1.004-4.796), PR - ER - AR- (HR = 2.316, 95% CI, 1.097-5.082) and PR - ER + AR- (HR = 2.928, 95% CI, 1.366-6.276) subgroups compared to the PR - ER - AR+ subgroup. Our classification could help predict patient clinical outcomes, guide individual treatments and stratify patients in future clinical trials.
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页数:9
相关论文
共 37 条
[1]   Is androgen receptor targeting an emerging treatment strategy for triple negative breast cancer? [J].
Anestis, Aristomenis ;
Karamouzis, Michalis V. ;
Dalagiorgou, Georgia ;
Papavassiliou, Athanasios G. .
CANCER TREATMENT REVIEWS, 2015, 41 (06) :547-553
[2]   Estrogen and progesterone receptor status and outcome in epithelial ovarian cancers and low malignant potential tumors [J].
Arias-Pulido, Hugo ;
Smith, Harriet O. ;
Joste, Nancy E. ;
Bocklage, Therese ;
Qualls, Clifford R. ;
Chavez, Allison ;
Prossnitz, Eric R. ;
Verschraegen, Claire F. .
GYNECOLOGIC ONCOLOGY, 2009, 114 (03) :480-485
[3]   Cancer of the ovary, fallopian tube, and peritoneum [J].
Berek, Jonathan S. ;
Crum, Christopher ;
Friedlander, Michael .
INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS, 2012, 119 :S118-S129
[4]  
Bowman A, 2002, CLIN CANCER RES, V8, P2233
[5]   Triple-negative breast cancers express receptors for luteinizing hormone-releasing hormone (LHRH) and respond to LHRH antagonist Cetrorelix with growth inhibition [J].
Buchholz, Stefan ;
Seitz, Stephan ;
Schally, Andrew V. ;
Engel, Joerg B. ;
Rick, Ferenc G. ;
Szalontay, Luca ;
Hohla, Florian ;
Krishan, Awtar ;
Papadia, Andrea ;
Gaiser, Timo ;
Brockhoff, Gero ;
Ortmann, Olaf ;
Diedrich, Klaus ;
Koester, Frank .
INTERNATIONAL JOURNAL OF ONCOLOGY, 2009, 35 (04) :789-796
[6]   Detection of gonadotropin-releasing hormone receptor and its mRNA in primary human epithelial ovarian cancers [J].
Chien, CH ;
Chen, CH ;
Lee, CYG ;
Chang, TC ;
Chen, RJ ;
Chow, SN .
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, 2004, 14 (03) :451-458
[7]   Progesterone-dependent regulation of female reproductive activity by two distinct progesterone receptor isoforms [J].
Conneely, OM ;
Mulac-Jericevic, B ;
Lydon, JP .
STEROIDS, 2003, 68 (10-13) :771-778
[8]   Hormone Receptor, HER2/NEU and EGFR Expression in Ovarian Carcinoma - is here a Prognostic Phenotype? [J].
Demir, Lutfiye ;
Yigit, Seyran ;
Sadullahoglu, Canan ;
Akyol, Murat ;
Cokmert, Suna ;
Kucukzeybek, Yuksel ;
Alacacioglu, Ahmet ;
Cakalagaoglu, Fulya ;
Tarhan, Mustafa Oktay .
ASIAN PACIFIC JOURNAL OF CANCER PREVENTION, 2014, 15 (22) :9739-9745
[9]   Combined Androgen and Estrogen Receptor Status in Breast Cancer: Treatment Prediction and Prognosis in a Population-Based Prospective Cohort [J].
Elebro, Karin ;
Borgquist, Signe ;
Simonsson, Maria ;
Markkula, Andrea ;
Jirstrom, Karin ;
Ingvar, Christian ;
Rose, Carsten ;
Jernstrom, Helena .
CLINICAL CANCER RESEARCH, 2015, 21 (16) :3640-3650
[10]   Targeted chemotherapy of endometrial, ovarian and breast cancers with cytotoxic analogs of luteinizing hormone-releasing hormone (LHRH) [J].
Engel, J. B. ;
Schally, A. V. ;
Buchholz, S. ;
Seitz, S. ;
Emons, G. ;
Ortmann, O. .
ARCHIVES OF GYNECOLOGY AND OBSTETRICS, 2012, 286 (02) :437-442