Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York.
University of Alabama at Birmingham, Birmingham, Alabama.
Cancer Med. 2018 Mar;7(3):616-625. doi: 10.1002/cam4.1335. Epub 2018 Feb 18.
The objective of this study was to investigate the relationship of insulin-like growth factor 2 (IGF2) expression and survival in women with uterine carcinosarcoma (UCS). Insulin-like growth factor 2 protein expression was determined by immunohistochemical staining of tumor tissues from 103 patients with UCS. The H-score (product of staining intensity and percentage positive cells) was quantified for the epithelial cytoplasmic (EC), epithelial nuclear (EN), and malignant stromal compartments. Multivariable Cox proportional hazard regression models were used to examine the relationship of IGF2 levels with progression-free survival (PFS) and overall survival (OS). Adjusting for stage, race, and adjuvant therapy, PFS and OS were reduced in patients with high IGF2 (H-score ≥ median) in the EC and EN compartments. Black race was independently associated with reduced PFS and OS in patients with early-stage disease, and IGF2 levels in the EC were higher in black than in white patients (P = 0.02, Wilcoxon test). In a race-stratified multivariable analysis, high IGF2 in the epithelial compartments more than doubled the risk of death in black women; HR = 2.43 (95% CI: 1.18-5.01, P = 0.02) for high IGF2 in the EC; and HR = 2.34 (95% CI: 1.25-4.39, P = 0.008) for high IGF2 in the EN. In conclusion, high tumor IGF2 expression is an independent risk factor for reduced PFS and OS in UCS. Black women have elevated tumor IGF2 compared with white women, and decreased survival associated with high IGF2. These findings identify IGF2 as a candidate biomarker for survival linked to racial disparity in women with UCS.
本研究旨在探讨胰岛素样生长因子 2（IGF2）表达与子宫癌肉瘤（UCS）患者生存的关系。通过免疫组织化学染色检测 103 例 UCS 患者肿瘤组织中的 IGF2 蛋白表达。上皮细胞质（EC）、上皮核（EN）和恶性间质部分的 H 评分（染色强度和阳性细胞百分比的乘积）进行量化。多变量 Cox 比例风险回归模型用于研究 IGF2 水平与无进展生存期（PFS）和总生存期（OS）的关系。调整分期、种族和辅助治疗后，EC 和 EN 中 IGF2 高（H 评分≥中位数）的患者 PFS 和 OS 降低。黑种人独立与早期疾病患者的 PFS 和 OS 降低相关，EC 中的 IGF2 水平在黑种人患者中高于白种人患者（P=0.02，Wilcoxon 检验）。在按种族分层的多变量分析中，上皮细胞中 IGF2 高增加了黑人女性死亡的风险；EC 中 IGF2 高的 HR=2.43（95%CI：1.18-5.01，P=0.02）；EN 中 IGF2 高的 HR=2.34（95%CI：1.25-4.39，P=0.008）。总之，肿瘤 IGF2 高表达是 UCS 患者 PFS 和 OS 降低的独立危险因素。与白人女性相比，黑人女性肿瘤 IGF2 水平较高，与 IGF2 高相关的生存降低。这些发现表明 IGF2 可作为与 UCS 患者种族差异相关的生存候选生物标志物。
