Lozneanu Ludmila, Pinciroli Patrizia, Ciobanu Delia Apostol, Carcangiu Maria Luisa, Canevari Silvana, Tomassetti Antonella, Căruntu Irina-Draga
Department of Morphofunctional Sciences - Histology, Pathology, "Grigore T. Popa" University of Medicine and Pharmacy, Iassy, Romania Department of Experimental Oncology and Molecular Medicine - Unit of Molecular Therapies, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Department of Experimental Oncology and Molecular Medicine - Unit of Molecular Therapies, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Anticancer Res. 2016 Aug;36(8):4155-63.
BACKGROUND/AIM: The activation of the membrane tyrosine kinase AXL is implicated in the migration and invasion in several carcinomas, including ovarian cancer. Herein, we investigated the association of the expression of AXL transcript and protein to the aggressiveness of ovarian cancer, as well as to patient outcome.
Overall and relapse-free survival were determined with respect to AXL transcript levels by computational analysis on two publicly available datasets containing data of gene expression from high-grade ovarian cancers (n=776). Immunohistochemical evaluation of AXL protein expression was then performed using a proprietary tissue microarray consisting of 62 ovarian cancers of different histology, grading and staging. Expression was analyzed for association with clinicopathological parameters, including survival.
In both analyzed datasets, AXL transcript expression was significantly associated to both overall and relapse-free survival in high-grade ovarian cancers. Membrane expression of AXL protein was observed in 89% of the analyzed ovarian cancers. A significant correlation was found between AXL expression and serous histologic subtype, higher tumor grade and type II tumors. No significant association between AXL protein expression and patient survival was found in our cohort. AXL is frequently expressed in high-grade serous ovarian cancers and its expression is significantly associated to tumors displaying poor prognosis.
AXL is a potential prognostic marker for the most aggressive ovarian carcinomas.
背景/目的:膜酪氨酸激酶AXL的激活与包括卵巢癌在内的多种癌症的迁移和侵袭有关。在此,我们研究了AXL转录本和蛋白表达与卵巢癌侵袭性以及患者预后的关系。
通过对两个公开可用数据集进行计算分析,根据AXL转录本水平确定总生存期和无复发生存期,这两个数据集包含高级别卵巢癌(n = 776)的基因表达数据。然后使用由62例不同组织学、分级和分期的卵巢癌组成的专用组织微阵列对AXL蛋白表达进行免疫组织化学评估。分析表达与临床病理参数(包括生存)的相关性。
在两个分析的数据集中,AXL转录本表达与高级别卵巢癌的总生存期和无复发生存期均显著相关。在89%的分析卵巢癌中观察到AXL蛋白的膜表达。AXL表达与浆液性组织学亚型、更高的肿瘤分级和II型肿瘤之间存在显著相关性。在我们的队列中,未发现AXL蛋白表达与患者生存之间存在显著关联。AXL在高级别浆液性卵巢癌中经常表达,其表达与预后不良的肿瘤显著相关。
AXL是最具侵袭性的卵巢癌的潜在预后标志物。