Kanjanapan Yada, Deb Siddhartha, Young Richard J, Bressel Mathias, Mileshkin Linda, Rischin Danny, Hofman Michael S, Narayan Kailash, Siva Shankar
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
Department of Anatomical Pathology, Peter MacCallum Cancer Centre, Melbourne, Australia.
Clin Transl Radiat Oncol. 2017 Feb 8;2:53-58. doi: 10.1016/j.ctro.2017.01.003. eCollection 2017 Feb.
BACKGROUND/PURPOSE: Chemoradiation (CRT) is standard therapy for locally advanced cervical cancer (LACC). However, there is a lack of biomarkers to identify patients at high relapse-risk. We examine metabolic (glucose transporter-1 [Glut-1]), hypoxic (hypoxia inducible factor [HIF-1α]; carbonic anhydrase [CA-9]) and proliferative (Ki-67) markers for prognostic utility in LACC.
MATERIALS/METHODS: 60 LACC patients treated with CRT had pre-treatment biopsies. Immunohistochemistry was performed for Glut-1, HIF-1a and CA-9, to generate a histoscore from intensity and percentage staining; and Ki-67 scored by percentage of positive cells. For each biomarker, treatment response and survival was compared between low and high-staining groups by logrank testing and multivariate analyses.
High Glut-1 expression was associated with inferior progression-free survival (PFS), (hazard ratio [HR] 2.8, = 0.049) and overall survival (OS), (HR 5.0, = 0.011) on multifactor analysis adjusting for stage, node positivity, tumour volume and uterine corpus invasion. High Glut-1 correlated with increased risk of distant failure (HR 14.6, = 0.001) but not local failure. Low Glut-1 was associated with higher complete metabolic response rate on post-therapy positron emission tomography scan (odds ratio 3.4, = 0.048). Ki-67 was significantly associated with PFS only (HR 1.19 per 10 units increase, = 0.033). Biomarkers for hypoxia were not associated with outcome.
High Glut-1 in LACC is associated with poor outcome post CRT. If prospectively validated, Glut-1 may help select patients for more intensive treatment regimens.
背景/目的:放化疗(CRT)是局部晚期宫颈癌(LACC)的标准治疗方法。然而,目前缺乏能够识别高复发风险患者的生物标志物。我们研究了代谢标志物(葡萄糖转运蛋白1 [Glut-1])、缺氧标志物(缺氧诱导因子[HIF-1α];碳酸酐酶[CA-9])和增殖标志物(Ki-67)在LACC中的预后价值。
材料/方法:60例接受CRT治疗的LACC患者在治疗前进行活检。对Glut-1、HIF-1α和CA-9进行免疫组织化学检测,根据染色强度和百分比生成组织学评分;Ki-67根据阳性细胞百分比进行评分。对于每个生物标志物,通过对数秩检验和多变量分析比较低染色组和高染色组的治疗反应和生存率。
在多因素分析中,校正分期、淋巴结阳性、肿瘤体积和子宫体侵犯后,高Glut-1表达与无进展生存期(PFS)较差相关(风险比[HR] 2.8,P = 0.049)和总生存期(OS)较差相关(HR 5.0,P = 0.011)。高Glut-1与远处转移风险增加相关(HR 14.6,P = 0.001),但与局部复发无关。低Glut-1与治疗后正电子发射断层扫描的完全代谢缓解率较高相关(优势比3.4,P = 0.048)。Ki-67仅与PFS显著相关(每增加10个单位,HR 1.19,P = 0.033)。缺氧生物标志物与预后无关。
LACC中高Glut-1表达与CRT治疗后预后不良相关。如果前瞻性验证成立,Glut-1可能有助于选择更强化治疗方案的患者。