Androgen receptor status predicts development of brain metastases in ovarian cancers
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Gloria Mittica1,2,*, Rebecca Senetta3,*, Giulia Scotto1, Massimo Aglietta1,2, Furio Maggiorotto4, Eleonora Ghisoni1,2, Sofia Genta1,2, Renzo Boldorini5, Claudia Manini6, Isabella Morra7, Roberta Buosi8, Anna Sapino3,9, Paola Cassoni9,* and Giorgio Valabrega1,2,*
1Department of Oncology, University of Turin, Turin, Italy
2Division of Medical Oncology-1, Candiolo Cancer Institute-FPO- IRCCS, Candiolo, Italy
3Unit of Pathology Candiolo Cancer Institute-FPO- IRCCS, Candiolo, Italy
4Division of Gynecologic Oncology, Candiolo Cancer Institute-FPO- IRCCS, Candiolo, Italy
5Department of Health Science, University of Eastern Piedmont “Amedeo Avogadro”, Novara, Italy
6Unit of Pathology, Giovanni Bosco Hospital, Turin, Italy
7Unit of Pathology, Città della Salute e della Scienza, Turin, Italy
8Division of Oncology, Santo Spirito Hospital, Casale Monferrato, Italy
9Department of Medical Sciences, University of Turin, Turin, Italy
*These authors have contributed equally to this work
Giorgio Valabrega, email: [email protected]
Keywords: androgen receptor, ovarian cancer, brain metastases
Received: November 24, 2016 Accepted: March 17, 2017 Published: April 12, 2017
Brain metastases are uncommon localizations in epithelial ovarian cancer (EOC), their reported incidence is increasing and no predictive biomarkers have been identified yet. Goals of this study were: i) to define a possible association between Estrogen Receptor (ER), Progesterone Receptor (PR), Androgen Receptor (AR),human EGF receptor 2 (HER2) and brain progression in EOC patients, and ii) to identify differences in ER, PR, AR and HER2 protein expression from primary EOC and its matched resected brain metastasis. A retrospective series of 11 EOC with matched brain metastasis surgically removed was collected. For comparison, a “Control dataset” of 22 patients, without evidence of brain involvement after an adequate follow up was matched. ER, PR, AR and HER2 status were analyzed by means of immunohistochemistry forCases (both primary and metastatic lesions) and Controls.
Univariate analysis showed that AR status was significantly associated with brain localization, both considered as discrete variable (cut-off: 10%, p=0.013) and as continuous one (p=0.035). Multivariate analysis confirmed this trend (p=0.053). When considered as continuous variables, ER and AR showed greater expression in primary tumors in comparison with brain metastases (p=0.013 and p=0.032, respectively).
In our series, AR predicts brain involvement, with a 9.5 times higher propensity for AR-negative EOC. Moreover, brain dissemination is probably the result of progressive dedifferentiation of primary tumor, shown by reduction of ER and AR expression in metastases. Further studies are required, in order to anticipate and improve multimodal treatment of brain metastases.
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