Davidson Ben, Hellesylt Ellen, Holth Arild, Danielsen Håvard Emil, Skeie-Jensen Tone, Katz Betina
Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, N-0424, Oslo, Norway.
Institute for Clinical Medicine, the Medical Faculty, University of Oslo, N-0316, Oslo, Norway.
Virchows Arch. 2017 Sep;471(3):355-362. doi: 10.1007/s00428-017-2172-5. Epub 2017 Jun 22.
The objective of this study was to validate the diagnostic and clinical role of four protein products of genes previously found to be differentially expressed in uterine low-grade endometrial stromal sarcoma (LG-ESS) compared to uterine leiomyosarcoma (LMS). Protein expression by immunohistochemistry of transgelin (TGLN), neuron navigator-2 (NAV2), fatty acid binding protein-3 (FABP3), and cyclin D2 (CCND2) was analyzed in 305 uterine sarcomas (231 LMS, 74 LG-ESS). Expression was analyzed for association with clinicopathologic parameters and survival. TGLN (p < 0.001), NAV2 (p < 0.001), and FABP3 (p = 0.005) were overexpressed in LMS compared to LG-ESS, whereas nuclear CCND2 (p < 0.001) was overexpressed in LG-ESS. NAV2 expression was associated with shorter overall survival in patients with LMS (p = 0.037), whereas nuclear CCND2 expression in LG-ESS was significantly related to longer survival (p = 0.012) in univariate analysis. Nuclear CCND2 expression was an independent prognosticator in Cox multivariate analysis (p = 0.023). In conclusion, TGLN, FABP3, NAV2, and nuclear CCND2 aid in differentiating LG-ESS from LMS. NAV2 and CCND2 are novel candidate prognostic markers in LMS and LG-ESS, respectively.
本研究的目的是验证先前发现的与子宫平滑肌肉瘤(LMS)相比,在子宫低级别子宫内膜间质肉瘤(LG-ESS)中差异表达的4种基因的蛋白质产物的诊断和临床作用。通过免疫组织化学分析了305例子宫肉瘤(231例LMS,74例LG-ESS)中反式肌动蛋白(TGLN)、神经导航蛋白-2(NAV2)、脂肪酸结合蛋白-3(FABP3)和细胞周期蛋白D2(CCND2)的蛋白表达。分析了表达与临床病理参数及生存的相关性。与LG-ESS相比,TGLN(p < 0.001)、NAV2(p < 0.001)和FABP3(p = 0.005)在LMS中过表达,而核CCND2(p < 0.001)在LG-ESS中过表达。NAV2表达与LMS患者较短的总生存期相关(p = 0.037),而在单因素分析中,LG-ESS中核CCND2表达与较长生存期显著相关(p = 0.012)。在Cox多因素分析中,核CCND2表达是独立的预后因素(p = 0.023)。总之,TGLN、FABP3、NAV2和核CCND2有助于鉴别LG-ESS与LMS。NAV2和CCND2分别是LMS和LG-ESS中新的候选预后标志物。