Expression of FAP in Lung Cancer and Its Correlation With the Tumor Glucose Metabolism and the Histopathology

Purpose To explore the expression of fibroblast activation protein (FAP) in lung cancer (LC) and its correlation with tumor glucose metabolism and histopathology.Methods From June 2018 to November 2020, a total of 73 patients with newly diagnosed LC were included. Immunohistochemical staining was used to quantify the FAP expression in the tumors. The histopathological type and tumor grade were determined on the histopathological examination. Tumor glucose metabolic parameters and tumor maximal diameter were measured on [18F] F-FDG PET/CT. Univariate and multivariate analysis were used to study the correlation between FAP expression level and glucose metabolic variables and various histopathology.Results Positive FAP expression was observed in 97.3% (71/73) of LC lesions, which was significantly higher than 87.7% (64/73) of [18F] F-FDG positivity on PET/CT (χ2=4.818, P=0.028). In 12 early adenocarcinomas (ADCs), only 3 lesions (25%) were positive on PET/CT, however, 10 lesions (83.3%) were positive with FAP expression. When FAP expression was classified to low level (scores≤3) and high level (scores>4), high FAP level was found in 80.8% tumors and low FAP level in other 19.2% tumors. High FAP level was identified in 100.0% of squamous cell carcinoma (SCC), 85.7% of ADCs, 66.7% (4/6) of large cell neuroendocrine carcinoma (LCNC) and 40.0% (4/10) of small cell lung cancer (SCLC)(P<0.05). In the non-mucinous ADC lesions, on univariate analysis, FAP expression level showed close relationships with tumor metabolism parameters (SUVmax, SUVmean, and TLG), tumor diameter, tumor grade and lesion attenuation (P<0.05).Conclusion The present study demonstrates that FAP expresses widely in LC and has a great variant level in different histopathological types. High positive rate of FAP expression implies FAP targeted imaging may be a sensitive modality for diagnosing LC, especially for early ADCs, and may serve as an alternative of [18F] F-FDG PET/CT.