Pham Deborah L, Scheble Veit, Bareiss Petra, Fischer Anna, Beschorner Christine, Adam Annemarie, Bachmann Cornelia, Neubauer Hans, Boesmueller Hans, Kanz Lothar, Wallwiener Diethelm, Fend Falko, Lengerke Claudia, Perner Sven, Fehm Tanja, Staebler Annette
Institute of Pathology, University of Tuebingen, Tuebingen, Germany.
Int J Gynecol Pathol. 2013 Jul;32(4):358-67. doi: 10.1097/PGP.0b013e31826a642b.
The transcription factor SOX2 has been extensively studied for its role in embryonic stem cell self-renewal and pluripotency. More recent data suggest oncogenic functions of SOX2 and demonstrate expression in several carcinoma types, predominantly of squamous cell origin. The gene SOX2 is located at chromosome 3q26, a region that is frequently amplified in ovarian high-grade serous carcinoma. In this study, we correlate SOX2 protein expression and gene-amplification status in ovarian carcinomas with histopathologic criteria and disease outcome. A total of 215 cases of ovarian carcinomas (154 serous, 39 endometrioid, 11 clear cell, 5 mucinous, and 6 transitional cell carcinomas) were analyzed by immunohistochemistry in a tissue microarray for nuclear expression of SOX2. A total of 60.5% of all carcinomas showed SOX2 expression with no significant difference between the major histologic types. Interestingly, SOX2 expression was predominantly a feature of high-grade tumors (G1: 36.4%, G2: 55.6%, G3: 64.0%, P=0.040). In 21.2% of these cases, fluorescence in situ hybridization analysis detected low-level SOX2 gene amplification which was not significantly associated with SOX2 protein expression. However, survival analysis of Stage II to IV high-grade serous carcinomas revealed a favorable effect of SOX2 expression (median disease-free survival 27 vs. 21 mo, P=0.041; median overall survival 39 vs. 25 mo, P=0.062). Further studies are needed to explore whether expression of SOX2 has a specific role in prognosis and therapy response.
转录因子SOX2因其在胚胎干细胞自我更新和多能性中的作用而受到广泛研究。最近的数据表明SOX2具有致癌功能,并在几种主要为鳞状细胞起源的癌组织类型中表达。SOX2基因位于3q26染色体上,该区域在卵巢高级别浆液性癌中经常发生扩增。在本研究中,我们将卵巢癌中SOX2蛋白表达和基因扩增状态与组织病理学标准及疾病转归进行关联分析。通过组织芯片免疫组化分析215例卵巢癌(154例浆液性癌、39例子宫内膜样癌、11例透明细胞癌、5例黏液性癌和6例移行细胞癌)中SOX2的核表达情况。所有癌组织中共有60.5%显示SOX2表达,各主要组织学类型之间无显著差异。有趣的是,SOX2表达主要是高级别肿瘤的特征(G1:36.4%,G2:55.6%,G3:64.0%,P = 0.040)。在这些病例中,21.2%通过荧光原位杂交分析检测到低水平的SOX2基因扩增,其与SOX2蛋白表达无显著相关性。然而,对II至IV期高级别浆液性癌的生存分析显示SOX2表达具有有利影响(无病生存期中位数27个月对21个月,P = 0.041;总生存期中位数39个月对25个月,P = 0.062)。需要进一步研究以探索SOX2表达在预后和治疗反应中是否具有特定作用。