Tüzüner Mete Bora, Öztürk Tülin, Eronat Allison Pınar, Seyhan Fatih, Kısakesen Halil İbrahim, Calay Zerrin, İlvan Şennur, Turna Hande, Yılmaz-Aydoğan Hülya, Bermek Hakan, Öztürk Oğuz
Department of Molecular Biology and Genetics, Istanbul Technical University, Istanbul, Turkey.
Department of Pathology, Cerrahpasa Medical School, Istanbul, Turkey.
Biochem Genet. 2016 Dec;54(6):784-802. doi: 10.1007/s10528-016-9756-7. Epub 2016 Jun 30.
There is growing attention focused on local estrogen production in the breast tissue and its possible role in breast cancer initiation and progression. Understanding the underlying mechanisms for estrogen synthesis and the microenvironment consisting of tumor and its surrounding adipose tissue might open new avenues in breast cancer prevention, prognosis and treatment. In order to obtain insight, we compared peritumoral and tumor tissue expressions of CYP17A1 and CYP19A1 genes, which play an important role in estrogen biosynthesis. The paired tissue samples of 20 postmenopausal ER/PR patients diagnosed with invasive ductal breast cancer were studied. In addition, 12 breast tissue samples obtained from premenopausal women without a history of breast cancer were also investigated as representative of normal conditions. Peritumoral adipose tissues expressed CYP19A1 approximately threefold higher than tumor itself (p = 0.001). A nonsignificant trend toward low expression of CYP17A1 was observed in peritumoral compared to tumor tissue (p = 0.687). Clinicopathological parameters and patient characteristics which are accepted as risk factors for breast cancer were also associated with individual and combined expressions of CYP17A1 and CYP19A1. This study offers that evaluation of CYP17A1 and CYP19A1 local expression levels might be useful for deciding on personalized treatment approaches and more accurate diagnosis, when evaluated together with several clinicopathological and disease risk factors. Considering the key role of these CYPs in estrogen synthesis, determining their expression levels may be useful as a postdiagnostic marker and for choosing the right treatment method in addition to the conventional approach.
乳腺组织中局部雌激素生成及其在乳腺癌发生和发展中可能发挥的作用正受到越来越多的关注。了解雌激素合成的潜在机制以及由肿瘤及其周围脂肪组织组成的微环境,可能为乳腺癌的预防、预后和治疗开辟新途径。为了深入了解,我们比较了在雌激素生物合成中起重要作用的CYP17A1和CYP19A1基因在肿瘤周围组织和肿瘤组织中的表达情况。对20例诊断为浸润性导管癌的绝经后ER/PR患者的配对组织样本进行了研究。此外,还对12例无乳腺癌病史的绝经前女性的乳腺组织样本进行了调查,作为正常情况的代表。肿瘤周围脂肪组织中CYP19A1的表达比肿瘤本身高约三倍(p = 0.001)。与肿瘤组织相比,肿瘤周围组织中CYP17A1表达呈低表达趋势,但无统计学意义(p = 0.687)。被认为是乳腺癌危险因素的临床病理参数和患者特征也与CYP17A1和CYP19A1的个体及联合表达相关。本研究表明,在与多种临床病理和疾病危险因素一起评估时,评估CYP17A1和CYP19A1的局部表达水平可能有助于确定个性化治疗方案和更准确的诊断。考虑到这些细胞色素在雌激素合成中的关键作用,除了传统方法外,确定它们的表达水平可能作为诊断后标志物和选择正确治疗方法有用。