Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan; Department of Thoracic Surgery, National Cancer Center Hospital, Kashiwa, Chiba, Japan; Departments of General Thoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Department of Thoracic Surgery, National Cancer Center Hospital, Kashiwa, Chiba, Japan.
Lung Cancer. 2019 Oct;136:57-64. doi: 10.1016/j.lungcan.2019.08.003. Epub 2019 Aug 9.
The purpose of this study was to investigate whether fluorodeoxyglucose (FDG) accumulation is associated with the expression of microenvironmental factors in radiological pure-solid lung adenocarcinoma.
We selected 50 cases involving patients with clinical stage IA radiological pure-solid lung adenocarcinoma who were examined with 18 F-FDG positron emission tomography (18 F-FDG PET) prior to surgery and whose FDG-PET maximal standardized uptake values (SUVmax) were calculated. Tumor specimens were analyzed by immunohistochemistry (IHC) for phosphorylated AKT (pAKT), glucose transporter type 1 (GLUT-1), carbonic anhydrase IX (CA IX), podoplanin-positive cancer associated fibroblasts (PDPN + CAFs), and CD204-positive tumor-associated macrophages (CD204+ TAMs). We compared the clinicopathological characteristics and the immunophenotypes between two groups with high and low SUVmax.
A multivariate analysis revealed that SUVmax was an independently significant prognostic factor (P = .03). The 5-year overall survival (OS) and recurrence free survival (RFS) rates of the SUV max high and low groups were 68.0% versus 100% ((P = .002; OS) 54.3% versus 90.8% (P < .001; RFS)), respectively. Vascular invasion, pleural invasion, and the prevalence of solid predominant subtype tumors were more frequent in the SUVmax high group. Additionally, the expression levels of GLUT-1 and pAKT in cancer cells were significantly higher in this group (P < .001, and P < .001 respectively). Furthermore, the numbers of the tumor-promoting stromal cells, i.e., PDPN + CAFs and CD204+ TAMs, were also significantly higher in the SUVmax high group (P = .001, and P < .001 respectively).
Our results indicated that a close association exists between the SUVmax and expressions of not only metabolism associated markers in cancer cells but also of tumor promoting markers in stromal cells among patients with clinical stage IA adenocarcinoma with radiologically pure-solid nodules.
本研究旨在探讨氟脱氧葡萄糖(FDG)摄取与影像学纯磨玻璃密度肺腺癌中微环境因子的表达是否相关。
我们选择了 50 例临床ⅠA 期影像学纯磨玻璃密度肺腺癌患者,这些患者在手术前均进行了 18F-FDG 正电子发射断层扫描(18F-FDG PET)检查,并计算了 FDG-PET 最大标准化摄取值(SUVmax)。通过免疫组织化学(IHC)分析肿瘤标本,检测磷酸化 AKT(pAKT)、葡萄糖转运蛋白 1(GLUT-1)、碳酸酐酶 IX(CAIX)、足突蛋白阳性癌相关成纤维细胞(PDPN+CAFs)和 CD204 阳性肿瘤相关巨噬细胞(CD204+TAMs)的表达。我们比较了 SUVmax 高、低两组的临床病理特征和免疫表型。
多因素分析显示,SUVmax 是一个独立的显著预后因素(P=0.03)。SUVmax 高、低两组的 5 年总生存率(OS)和无复发生存率(RFS)分别为 68.0%与 100%(P=0.002;OS)、54.3%与 90.8%(P<0.001;RFS)。SUVmax 高组中血管侵犯、胸膜侵犯和实性为主型肿瘤的比例较高。此外,该组中癌细胞的 GLUT-1 和 pAKT 表达水平显著升高(P<0.001 和 P<0.001)。此外,SUVmax 高组中促肿瘤间质细胞,即 PDPN+CAFs 和 CD204+TAMs 的数量也显著增加(P=0.001 和 P<0.001)。
我们的研究结果表明,在临床ⅠA 期伴影像学纯磨玻璃密度结节的腺癌患者中,SUVmax 与癌细胞代谢相关标志物的表达以及间质细胞促肿瘤标志物的表达密切相关。