Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Dec 12;17(1):195.
doi: 10.1186/s12890-017-0534-z.

Napsin A levels in epithelial lining fluid as a diagnostic biomarker of primary lung adenocarcinoma

Akifumi Uchida  1 , Takuya Samukawa  1 , Tomohiro Kumamoto  1 , Masahiro Ohshige  1 , Kazuhito Hatanaka  2 , Yoshihiro Nakamura  3 , Keiko Mizuno  1 , Ikkou Higashimoto  1 , Masami Sato  3 , Hiromasa Inoue  4
Affiliations

Napsin A levels in epithelial lining fluid as a diagnostic biomarker of primary lung adenocarcinoma

Akifumi Uchida et al. BMC Pulm Med. .

Abstract

Background: It is crucial to develop novel diagnostic approaches for determining if peripheral lung nodules are malignant, as such nodules are frequently detected due to the increased use of chest computed tomography scans. To this end, we evaluated levels of napsin A in epithelial lining fluid (ELF), since napsin A has been reported to be an immunohistochemical biomarker for histological diagnosis of primary lung adenocarcinoma.

Methods: In consecutive patients with indeterminate peripheral lung nodules, ELF samples were obtained using a bronchoscopic microsampling (BMS) technique. The levels of napsin A and carcinoembryonic antigen (CEA) in ELF at the nodule site were compared with those at the contralateral site. A final diagnosis of primary lung adenocarcinoma was established by surgical resection.

Results: We performed BMS in 43 consecutive patients. Among patients with primary lung adenocarcinoma, the napsin A levels in ELF at the nodule site were markedly higher than those at the contralateral site, while there were no significant differences in CEA levels. Furthermore, in 18 patients who were undiagnosed by bronchoscopy and finally diagnosed by surgery, the napsin A levels in ELF at the nodule site were identically significantly higher than those at the contralateral site. In patients with non-adenocarcinoma, there were no differences in napsin A levels in ELF. The area under the receiver operator characteristic curve for identifying primary lung adenocarcinoma was 0.840 for napsin A and 0.542 for CEA.

Conclusion: Evaluation of napsin A levels in ELF may be useful for distinguishing primary lung adenocarcinoma.

Keywords: Biomarkers; Bronchoscopy; Epithelial lining fluid; Lung cancer diagnosis; Primary lung adenocarcinoma.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the institutional review board of Kagoshima University Medical and Dental Hospital and the committee’s reference number was 24-71. Written informed consent for this study was obtained before bronchoscopy.

Consent for publication

Witten informed consent for publication of all images in this manuscript was obtained from the patients.

Competing interests

Hiromasa Inoue reports grants from Astellas, AstraZeneca, Boehringer-Ingelheim, ChugaiPharm, GlaxoSmithKline, Pfizer, MerckSharp&Dohme, Teijin-Pharma, Torii, personal fees from Astellas, AstraZeneca, Boehringer-Ingelheim, Chugai-Pharm, GlaxoSmithKline, Kyorin, MerckSharp&Dohme, MeijiSeikaPharma, Novartis, Otsuka, Pfizer, outside the submitted work.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Bronchoscopic microsampling (BMS) procedure. The BMS probe consists of a polyethylene outer sheath (black arrowhead) and an inner cotton fiber rod probe attached to a 30-mm-long stainless steel guide wire (white arrowhead). The probe is guided to the affected lesion in the subsegmental bronchus thorough the bronchoscope channel and the inner fiber rod probe (white arrowhead) is placed on the bronchial membrane as near as possible to the lung nodule. BMS: bronchoscopic maicrosampling
Fig. 2
Fig. 2
Computed tomography (CT) and immunohistological findings in a representative case. a A lung CT image shows a 20-mm, partly solid, ground-glass opacity nodule (arrowhead) in the right upper lobe. b Minimally invasive adenocarcinoma. The cancer demonstrates predominant lepidic growth with <5-mm invasion. The cancer cells have polygonal cytoplasm and atypical nuclei (inset) (hematoxylin-eosin staining, original magnification ×40 and high magnification ×100). c Immunohistological staining for napsin A. Napsin A is strongly positive in adenocarcinoma cells (inset for greater detail) (original magnification ×40 and high magnification ×100). d Immunohistological staining for CEA. CEA is strongly positive in adenocarcinoma cells (inset for greater detail) (original magnification ×40 and high magnification ×100). CT: computed tomography; CEA: carcinoembryonic antigen
Fig. 3
Fig. 3
Values of napsin A and CEA in ELF in the patients with primary lung adenocarcinoma. a Levels of napsin A in ELF (ELF-napsin A) in the patients with primary lung adenocarcinoma (n = 29, P < 0.001). b Values of CEA in ELF (ELF-CEA) in the patients with primary lung adenocarcinoma (n = 29, P = 0.634). c ELF-napsin A in the patients with primary lung adenocarcinoma who were undiagnosed by bronchoscopy and finally diagnosed by surgery (n = 18, P = 0.001). d ELF-CEA in the patients with primary lung adenocarcinoma who were undiagnosed by bronchoscopy and finally diagnosed by surgery (n = 18, P = 0.571). CEA: carcinoembryonic antigen; ELF: epithelial lining fluid
Fig. 4
Fig. 4
Napsin A levels in ELF in patients with primary lung adenocarcinoma and those with non-adenocarcinoma. a Values of napsin A in ELF (ELF-napsin A) in the patients with non-adenocarcinoma (n = 6, P = 0.463). b ELF-napsin A at the nodule site in primary lung adenocarcinoma (n = 29) and in non-adenocarcinoma (n = 6) (P = 0.024). ELF: epithelial lining fluid
Fig. 5
Fig. 5
Correlations of levels of napsin A in ELF. a Correlation between the levels of napsin A in ELF (ELF-napsin A) and the serum levels of napsin A (serum-napsin A) (n = 28, P = 0.916, r = 0.021). b Correlation between ELF-napsin A and the tumour size at surgery (n = 29, P = 0.053, r = 0.362). ELF: epithelial lining fluid
Fig. 6
Fig. 6
Receiver operating characteristic (ROC) curve for napsin A and CEA in ELF. The ROC curves for napsin A in ELF (ELF-napsin A, solid line) and CEA in ELF (ELF-CEA, dashed line). The areas under the ROC curves are 0.840 for ELF-napsin A and 0.542 for ELF-CEA
See this image and copyright information in PMC

References

    1. World Health Organization. Cancer. Fact Sheet Number 297. www.who.int/mediacentre/factsheets/fs297/en/ Last updated February 2015. Accessed 10 Feb 2015.
    1. Kennedy GT, Okusanya OT, Keating JJ, Heitjan DF, Deshpande C, Litzky LA, Albelda SM, Drebin JA, Nie S, Low PS, et al. The optical biopsy: a novel technique for rapid Intraoperative diagnosis of primary pulmonary Adenocarcinomas. Ann Surg. 2015;262(4):602–609. doi: 10.1097/SLA.0000000000001452. - DOI - PMC - PubMed
    1. Lim HJ, Ahn S, Lee KS, Han J, Shim YM, Woo S, Kim JH, Yie M, Lee HY, Yi CA. Persistent pure ground-glass opacity lung nodules >/= 10 mm in diameter at CT scan: histopathologic comparisons and prognostic implications. Chest. 2013;144(4):1291–1299. doi: 10.1378/chest.12-2987. - DOI - PubMed
    1. Slatore CG, Horeweg N, Jett JR, Midthun DE, Powell CA, Wiener RS, Wisnivesky JP, Gould MK. An official American Thoracic Society research statement: a research framework for pulmonary nodule evaluation and management. Am J Respir Crit Care Med. 2015;192(4):500–514. doi: 10.1164/rccm.201506-1082ST. - DOI - PMC - PubMed
    1. Okada M, Nishio W, Sakamoto T, Uchino K, Yuki T, Nakagawa A, Tsubota N. Prognostic significance of perioperative serum carcinoembryonic antigen in non-small cell lung cancer: analysis of 1,000 consecutive resections for clinical stage I disease. Ann Thorac Surg. 2004;78(1):216–221. doi: 10.1016/j.athoracsur.2004.02.009. - DOI - PubMed