Nanfang PET Center, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, Guangdong Province, China.
Eur J Nucl Med Mol Imaging. 2022 Jul;49(8):2938-2948. doi: 10.1007/s00259-022-05754-4. Epub 2022 Mar 7.
To explore the expression of fibroblast activation protein (FAP) in lung cancer (LC) and its correlation with tumor glucose metabolism and histopathology.
From 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 [F] 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.
Positive FAP expression was observed in 97.3% (71/73) LC lesions, which was significantly higher than 87.7% (64/73) of [F] F-FDG positivity observed on PET/CT (χ = 4.818, P = 0.028). In 12 early adenocarcinomas (ADCs), only three lesions (25%) were positive for [F] 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).
The 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.
探讨成纤维细胞激活蛋白（FAP）在肺癌（LC）中的表达及其与肿瘤葡萄糖代谢和组织病理学的相关性。
本研究纳入了 2018 年 6 月至 2020 年 11 月期间 73 例新诊断为 LC 的患者。采用免疫组织化学染色法对肿瘤中的 FAP 表达进行定量。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 [F] F-FDG PET/CT 测量肿瘤葡萄糖代谢参数和肿瘤最大直径。采用单因素和多因素分析研究 FAP 表达水平与葡萄糖代谢变量和肿瘤组织病理学的相关性。
在 73 例 LC 病变中，97.3%（71/73）的病变呈 FAP 阳性表达，明显高于 PET/CT 上观察到的 [F] F-FDG 阳性率 87.7%（64/73）（χ²=4.818，P=0.028）。在 12 例早期腺癌（ADC）中，仅 3 个病变（25%）在 PET/CT 上呈 [F] F-FDG 阳性，而 10 个病变（83.3%）呈 FAP 阳性。当将 FAP 表达分为低水平（评分≤3）和高水平（评分>4）时，高 FAP 水平见于 80.8%的肿瘤，低 FAP 水平见于其余 19.2%的肿瘤。鳞状细胞癌（SCC）中高 FAP 水平为 100.0%，ADC 为 85.7%，大细胞神经内分泌癌（LCNC）为 66.7%（4/6），小细胞肺癌（SCLC）为 40.0%（4/10）（P<0.05）。在非黏液性 ADC 病变中，单因素分析显示，FAP 表达水平与肿瘤代谢参数（最大标准摄取值（SUVmax）、平均标准摄取值（SUVmean）和总病灶糖酵解（TLG））、肿瘤直径、肿瘤分级和病灶衰减密切相关（P<0.05）。
本研究表明 FAP 在 LC 中广泛表达，在不同组织病理学类型中表现出很大的差异。FAP 表达的高阳性率表明 FAP 靶向成像可能是诊断 LC 的一种敏感方法，尤其是在早期 ADC 中。需要进一步使用此类探针进行验证。
