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Expression of fibroblast activation protein in lung cancer and its correlation with tumor glucose metabolism and histopathology

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

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, 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.

Results

Positive 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).

Conclusion

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.

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Data availability

All data were transparent. The data used in the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We are grateful to Prof Deng Yongjian, a pathologist, and his team in Nanfang Hospital, for providing direction in pathologic diagnoses and immunohistochemical staining and scores.

Funding

This work was supported financially by the National Science Foundation of China under grants 81873905.

Author information

Author notes

  1. Xiaohui Chen, Xinran Liu and Lijuan Wang contributed equally to this work

Authors and Affiliations

  1. Nanfang PET Center, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, Guangdong Province, China

    Xiaohui Chen, Xinran Liu, Lijuan Wang, Wenlan Zhou, Yin Zhang, Ying Tian, Jianer Tan, Ye Dong, Lilan Fu & Hubing Wu

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  1. Xiaohui Chen
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Contributions

Conceptualization: Hubing Wu

Formal analysis and investigation: Xiaohui Chen, Xinran Liu, Lijuan Wang, Wenlan Zhou, Yin Zhang, Ying Tian, Jianer Tan, Ye Dong, Lilan Fu, Hubing Wu

Writing-original draft preparation: Xiaohui Chen, Xinran Liu, Lijuan Wang

Writing-review and editing: Hubing Wu

Funding acquisition: Hubing Wu

Supervision: Hubing Wu

All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hubing Wu.

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Ethical approval was waived by the local Ethics Committee of Southern Medical University in view of the retrospective nature of the study.

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Due to the retrospective nature of the study, informed consent was not obtained in the study.

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The authors declare no competing interests.

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This article is part of the Topical Collection on Oncology - Chest

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Chen, X., Liu, X., Wang, L. et al. Expression of fibroblast activation protein in lung cancer and its correlation with tumor glucose metabolism and histopathology. Eur J Nucl Med Mol Imaging 49, 2938–2948 (2022). https://doi.org/10.1007/s00259-022-05754-4

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  • DOI: https://doi.org/10.1007/s00259-022-05754-4

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