Cho Arthur, Hur Jin, Moon Yong Wha, Hong Sae Rom, Suh Young Joo, Kim Yun Jung, Im Dong Jin, Hong Yoo Jin, Lee Hye-Jeong, Kim Young Jin, Shim Hyo Sup, Lee Jae Seok, Kim Joo-Hang, Choi Byoung Wook
Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Department of Radiology, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea.
BMC Cancer. 2016 Mar 16;16:224. doi: 10.1186/s12885-016-2251-z.
EGFR mutation-induced cell proliferation causes changes in tumor biology and tumor metabolism, which may reflect tumor marker concentration and 18F-FDG uptake on PET/CT. Direct aspirates of primary lung tumors contain different concentrations of tumor markers than serum tumor markers, and may correlate better with EGFR mutation than serum tumor markers. The purpose of this study is to investigate an association between cytologic tumor markers and FDG uptake with EGFR mutation status in non-small cell lung cancer (NSCLC).
We prospectively collected tumor aspirates of 61 patients who underwent EGFR mutation analysis. Serum and cytologic CYFRA 21-1, CEA, and SCCA levels were measured and correlated with EGFR gene mutations. FDG PET/CT was performed on 58 patients for NSCLC staging, and SUV was correlated with EGFR mutation status.
Thirty (50%) patients had EGFR mutation and 57 patients had adenocarcinoma subtype. Univariate analysis showed that female gender, never smoker, high levels of cytologic CYFRA 21-1 (c-CYFRA) and lower maximum standard uptake value (SUVmax) were correlated with EGFR mutations. ROC generated cut-off values of 20.8 ng/ml for c-CYFRA and SUVmax of 9.6 showed highest sensitivity for EGFR mutation detection. Multivariate analysis revealed that female gender [hazard ratio (HR): 18.15, p = 0.025], higher levels of c-CYFRA (HR: 7.58, and lower SUVmax (HR: 0.08, p = 0.005) were predictive of harboring EGFR mutation.
The cytologic tumor marker c-CYFRA was positively associated with EGFR mutations in NSCLC. EGFR mutation-positive NSCLCs have relatively lower glycolysis compared with NSCLCs without EGFR mutation.
表皮生长因子受体（EGFR）突变诱导的细胞增殖会导致肿瘤生物学特性和肿瘤代谢发生变化，这可能反映在肿瘤标志物浓度及PET/CT上的18F-氟代脱氧葡萄糖（18F-FDG）摄取情况。原发性肺癌的直接抽吸物所含肿瘤标志物浓度与血清肿瘤标志物不同，且与EGFR突变的相关性可能优于血清肿瘤标志物。本研究旨在探讨非小细胞肺癌（NSCLC）中细胞学肿瘤标志物及FDG摄取与EGFR突变状态之间的关联。
我们前瞻性收集了61例行EGFR突变分析患者的肿瘤抽吸物。检测血清及细胞学的细胞角蛋白19片段（CYFRA 21-1）、癌胚抗原（CEA）和鳞状细胞癌抗原（SCCA）水平，并将其与EGFR基因突变进行相关性分析。58例患者接受了FDG PET/CT检查以进行NSCLC分期，标准化摄取值（SUV）与EGFR突变状态进行相关性分析。
30例（50%）患者存在EGFR突变，57例患者为腺癌亚型。单因素分析显示，女性、从不吸烟者、细胞学CYFRA 21-1（c-CYFRA）水平高及最大标准摄取值（SUVmax）较低与EGFR突变相关。ROC曲线得出c-CYFRA的截断值为20.8 ng/ml以及SUVmax为9.6时对EGFR突变检测的敏感性最高。多因素分析显示，女性[风险比（HR）：18.15，p = 0.025]、c-CYFRA水平较高（HR：7.58）及SUVmax较低（HR：0.08，p = 0.005）可预测存在EGFR突变。
在NSCLC中，细胞学肿瘤标志物c-CYFRA与EGFR突变呈正相关。与无EGFR突变的NSCLC相比，EGFR突变阳性的NSCLC糖酵解相对较低。
