Expression of fibroblast activation protein in lung cancer and its correlation with tumor glucose metabolism and histopathology
Expression of fibroblast activation protein in lung cancer and its correlation with tumor glucose metabolism and histopathology
复制标题
成纤维细胞活化蛋白在肺癌中的表达及其与肿瘤糖代谢及组织病理学的相关性
DOI：
10.1007/s00259-022-05754-4
复制
发表时间：
2022-03-07
影响因子：
9.1
通讯作者：
Wu, Hubing
中科院分区：
文献类型：
--
作者：
Chen, Xiaohui;Liu, Xinran;Wu, Hubing
目的探讨成纤维细胞活化蛋白（fibroblast activation protein，FAP）在肺癌（lung cancer，LC）中的表达及其与肿瘤糖代谢和组织病理学的相关性。免疫组织化学染色用于定量肿瘤中FAP的表达。通过组织病理学检查确定组织病理学类型和肿瘤分级。通过[18 F] F-FDG PET/CT测量肿瘤糖代谢参数和肿瘤最大直径。结果73例LC中FAP阳性表达率为97.3%（71/73），显著高于PET/CT上[18 F] FDG阳性表达率87.7%（64/73）（χ2= 4.818，P = 0.028）;在12例早期腺癌（ADC）中，PET/CT上只有3个病灶（25%）[18 F] F-FDG阳性;然而，10个病灶（83.3%）FAP阳性。FAP表达分为低水平（评分≤ 3）和高水平（评分> 4）时，80.8%的肿瘤FAP高表达，19.2%的肿瘤FAP低表达。FAP在鳞癌、腺癌、大细胞神经内分泌癌和小细胞肺癌中的阳性率分别为100.0%、85.7%、66.7%和40.0%（P< 0.05）。在非粘液性ADC病变中，单因素分析显示，FAP表达水平与肿瘤代谢参数密切相关（最大标准摄取值（SUVmax）、平均标准摄取值（SUVmean）和总病变糖酵解（TLG））、肿瘤直径、肿瘤分级，和病变衰减结论FAP在LC中广泛表达，且在不同病理类型LC中表达差异较大。FAP表达的高阳性率意味着FAP靶向成像可能是诊断LC，特别是早期ADC的敏感方式。需要对此类探头进行进一步验证。
PurposeTo explore the expression of fibroblast activation protein (FAP) in lung cancer (LC) and its correlation with tumor glucose metabolism and histopathology.MethodsFrom June 2018 to November 2020, 73 patients with newly diagnosed LC were included. Immunohistochemical staining was used to quantify FAP expression in tumors. The histopathological type and tumor grade were determined via histopathological examination. The tumor glucose metabolism parameters and tumor maximal diameter were measured via [18F] F-FDG PET/CT. Univariate and multivariate analysis were performed to study the correlation of FAP expression levels with glucose metabolism variables and tumor histopathology.ResultsPositive FAP expression was observed in 97.3% (71/73) LC lesions, which was significantly higher than 87.7% (64/73) of [18F] F-FDG positivity observed on PET/CT (χ2= 4.818,P= 0.028). In 12 early adenocarcinomas (ADCs), only three lesions (25%) were positive for [18F] F-FDG on PET/CT; however, 10 lesions (83.3%) were positive for FAP. When FAP expression was classified into low level (scores ≤ 3) and high level (scores > 4), high FAP level was found in 80.8% tumors and low FAP level in the other 19.2% tumors. High FAP level was identified in 100.0% of squamous cell carcinomas (SCCs), 85.7% of ADCs, 66.7% (4/6) of large cell neuroendocrine carcinomas (LCNCs), and 40.0% (4/10) of small cell lung cancers (SCLCs) (P< 0.05). In non-mucinous ADC lesions, on univariate analysis, FAP expression level showed a close relationship with tumor metabolism parameters (maximal standard uptake value (SUVmax), mean standard uptake value (SUVmean), and total lesion glycolysis (TLG)), tumor diameter, tumor grade, and lesion attenuation (P< 0.05).ConclusionThe present study demonstrates that FAP is widely expressed in LC and shows great variation in different histopathological types. A high positive rate of FAP expression implies that FAP-targeted imaging may be a sensitive modality for diagnosing LC, especially in early ADCs. Further validation with such probes is warranted.