Estrogen Receptor-β Affects the Prognosis of Human Malignant Mesothelioma

Abstract

Malignant pleural mesothelioma is an asbestos-related neoplasm with poor prognosis, refractory to current therapies, the incidence of which is expected to increase in the next decades. Female gender was identified as a positive prognostic factor among other clinical and biological prognostic markers for malignant mesothelioma, yet a role of estrogen receptors (ERs) has not been studied. Our goal was to investigate ERs expression in malignant mesothelioma and to assess whether their expression correlates with prognosis. Immunohistochemical analysis revealed intense nuclear ERB staining in normal pleura that was reduced in tumor tissues. Conversely, neither tumors nor normal pleura stained positive for ERA. Multivariate analysis of 78 malignant mesothelioma patients with pathologic stage, histologic type, therapy, sex, and age at diagnosis indicated that ERB expression is an independent prognostic factor of better survival. Moreover, studies in vitro confirmed that treatment with 17B-estradiol led to an ERB-mediated inhibition of malignant mesothelioma cell proliferation as well as p21 CIP1 and p27 KIP1 up-regulation. Consistently cell growth was suppressed by ERB overexpression, causing a G 2 -M-phase cell cycle arrest, paralleled by cyclin B1 and survivin down-regulation. Our data support the notion that ERB acting as a tumor suppressor is of high potential relevance to prediction of disease progression and to therapeutic response of malignant mesothelioma patients.

Cyclooxygenase-2, Epidermal Growth Factor Receptor, and Aromatase Signaling in Inflammation and Mesothelioma

“…The classic 67 kDa and a variant 46 kDa of ERa and 59 kDa of ERb were expressed in malignant mesothelioma cell lines. Recent data published in literature support our findings on gender role orientation in malignant mesothelioma pathogenesis (72). Metintas and colleagues compared the relative risk of malignant mesothelioma in men versus women following environmental exposure to asbestos in a rural area of Anatolia in Turkey, where MPM is a frequent cause of cancer death.…”

Steroid receptor expression in thymomas and thymic carcinomas

“…41 It has also been shown that ERb negatively affects malignant cell tumorigenesis. 19,42,43 Although to our knowledge the exact correlation between ERb expression and tumor progression in thymic epithelial tumors is still unclear, ERb is suggested as a potential target in the treatment of ERb-positive thymomas and thymic carcinomas.…”

“…[17][18][19] Therefore, it is important to examine the expression of GR and other steroid receptors in thymic tumors.…”

Sexual dimorphism in cancer

“…ERβ function is required for normal lung and colon morphogenesis 24,25 and its activation exerts beneficial consequences in experimental models of colon 95 , glioma 96 , mesothelioma 97 , renal cell carcinoma (RCC) 98 and T cell lymphoma 99 .…”