Department of Pathology, Fuzhou Pulmonary Hospital of Fujian, Fuzhou 350008, Fujian Province, China , wlpwcx1@163.com
Abstract: (293 Views)
Background:Accurate assessment of visceral pleural invasion (VPI) is important for lung cancer staging and prognosis, but distinguishing PL0 from PL1 can be difficult on conventional histology. We evaluated whether combined thyroid transcription factor-1 (TTF-1) immunohistochemistry and aldehyde fuchsin elastic staining, interpreted with preoperative computed tomography (CT), facilitates VPI assessment in lung adenocarcinoma. Materials and Methods: This retrospective study included 76 patients with surgically resected lung adenocarcinoma. Clinicopathological characteristics, immunohistochemical findings, pathological stage, VPI status, CT features, and recurrence outcomes were reviewed. Selected sections underwent combined TTF-1/aldehyde fuchsin double staining. Principal component analysis (PCA) and Mahalanobis distance analysis were performed as exploratory analyses. Results: The mean age was 62.0 ± 8.8 years; 58.4% were female and 31.2% had a smoking history. EGFR mutations were detected in 58.4% of tumors. VPI was identified in 75 of 76 evaluable cases (98.7%). Double staining demonstrated the relationship of TTF-1-positive tumor cells to the visceral pleural elastic lamina, distinguishing the single PL0 case from PL1 lesions. Three patients (3.9%) developed recurrence 14–19 months after surgery. The first three principal components explained 64.5% of total variance; the PL0 case had the greatest Mahalanobis distance, whereas recurrent cases were not multivariate outliers. Conclusion: Combined TTF-1 and aldehyde fuchsin staining permits simultaneous visualization of tumor cells and the pleural elastic layer and may serve as a practical adjunct for distinguishing PL0 from PL1 in lung adenocarcinoma. CT may provide complementary information in integrated VPI assessment.
1. 1. Guo L, Zhu C, Cai L, et al. (2024) Global burden of lung cancer in 2022 and projected burden in 2050. Chin Med J (Engl), 137(21): 2576-2582. [DOI:10.1097/CM9.0000000000003268]
2. Filho AM, Laversanne M, Ferlay J, et al. (2025) The GLOBOCAN 2022 cancer estimates: Data sources, methods, and a snapshot of the cancer burden worldwide. Int J Cancer, 156(7): 1336-1346. [DOI:10.1002/ijc.35278]
3. Ji Y, Zhang Y, Liu S, et al. (2025) The epidemiological landscape of lung cancer: current status, temporal trend and future projections based on the latest estimates from GLOBOCAN 2022. J Natl Cancer Cent, 5(3): 278-283. [DOI:10.1016/j.jncc.2025.01.003]
4. Nicholson AG, Tsao MS, Beasley MB, et al. (2022) The 2021 WHO classification of lung tumors: Impact of advances since 2015. J Thorac Oncol, 17(3): 362-384. [DOI:10.1016/j.jtho.2021.11.003]
5. Minamino F, Araujo P, Dambrosio P, et al. (2024) The association of visceral pleural invasion with skip N2 metastasis on clinical stage IA NSCLC. Clinics, 79: 100334. [DOI:10.1016/j.clinsp.2024.100334]
6. Wightman SC, Lee JY, Ding L, et al. (2022) Adjuvant chemotherapy for visceral pleural invasion in 3-4-cm non-small-cell lung cancer improves survival. Eur J Cardiothorac Surg, 62(1): ezab498. [DOI:10.1093/ejcts/ezab498]
7. Rami-Porta R and Eberhardt WEE (2018) Clinical implications of the innovations in the primary tumour and metastasis of the 8th edition of the TNM classification for lung cancer. J Thorac Dis, 10(Suppl 22): S2682-S2685. [DOI:10.21037/jtd.2018.03.100]
8. Okada S, Hattori A, Matsunaga T, et al. (2021) Prognostic value of visceral pleural invasion in pure-solid and part-solid lung cancer patients. Gen Thorac Cardiovasc Surg, 69(2): 303-310. [DOI:10.1007/s11748-020-01470-8]
9. Xie LW and Wang J (2021) Evaluating three elastic-fiber staining methods for detecting visceral pleural invasion in lung adenocarcinoma patients. Clin Lab, 67(7): 1570-1575. [DOI:10.7754/Clin.Lab.2020.200851]
10. Li S, Huang Y, Zhang L, et al. (2023) Clinical significance of dual-block elastic stain evaluating visceral pleural invasion in peripheral non-small cell lung cancer. Int J Surg Pathol, 31(2): 175-183. [DOI:10.1177/10668969221098089]
11. Onoda H, Higashi M, Murakami T, et al. (2021) Correlation between pleural tags on CT and visceral pleural invasion of peripheral lung cancer that does not appear touching the pleural surface. Eur Radiol, 31(12): 9022-9029. [DOI:10.1007/s00330-021-07869-y]
12. Shi J, Li F, Yang F, et al. (2021) The combination of computed tomography features and circulating tumor cells increases the surgical prediction of visceral pleural invasion in clinical T1N0M0 lung adenocarcinoma. Transl Lung Cancer Res, 10(11): 4266-4280. [DOI:10.21037/tlcr-21-896]
13. Nakra T, Singh V, Nambirajan A, et al. (2021) Correlation of TTF-1 immunoexpression and EGFR mutation spectrum in non-small cell lung carcinoma. J Pathol Transl Med, 55(4): 279-288. [DOI:10.4132/jptm.2021.05.10]
14. Guan L, Zhao X, Tang L, et al. (2021) Thyroid Transcription Factor-1: Structure, Expression, Function and Its Relationship with Disease. Biomed Res Int, 2021: 9957209. [DOI:10.1155/2021/9957209]
15. Shen G, Dong J, Xiang Z, et al. (2022) Double staining of elastic fibre and immunohistochemistry is helpful to differentiate pleural invasion of lung cancer. J Clin Pathol, 75(3): 215-216. [DOI:10.1136/jclinpath-2021-207779]
16. Travis WD, Brambilla E, Rami-Porta R, et al. (2008) Visceral pleural invasion: pathologic criteria and use of elastic stains: proposal for the 7th edition of the TNM classification for lung cancer. J Thorac Oncol, 3(12): 1384-1390. [DOI:10.1097/JTO.0b013e31818e0d9f]
17. Liang RB, Li P, Li BT, et al. (2021) Modification of pathologic T classification for non-small cell lung cancer with visceral pleural invasion: data from 1,055 cases of cancers ≤3 cm. Chest, 160(2): 754-764. [DOI:10.1016/j.chest.2021.03.022]
18. Yeh YC, Chiang CH, Hsu PK, et al. (2025) Tumor cell invasion of the external elastic lamina designates visceral pleural invasion and predicts poorer patient outcomes in pulmonary nonmucinous invasive adenocarcinoma. J Thorac Oncol, 20(12): 1791-1800. [DOI:10.1016/j.jtho.2025.08.005]
19. Wang F, Li P, Li F (2021) Nomogram for predicting the relationship between the extent of visceral pleural invasion and survival in non-small-cell lung cancer. Can Respir J, 2021: 8816860. [DOI:10.1155/2021/8816860]
20. Neri S, Menju T, Sowa T, et al. (2019) Prognostic impact of microscopic vessel invasion and visceral pleural invasion and their correlations with epithelial-mesenchymal transition, cancer stemness, and treatment failure in lung adenocarcinoma. Lung Cancer, 128: 13-19. [DOI:10.1016/j.lungcan.2018.12.001]
21. Ozden S, Gokdemir I, Kiyik M (2024) The relationship between the degree of visceral pleural invasion and survival in non-small cell lung cancer. North Clin Istanb, 11(5): 367-372. [DOI:10.14744/nci.2023.25349]
22. Huang W, Deng HY, Lin MY, et al. (2022) Treatment modality for stage IB peripheral non-small cell lung cancer with visceral pleural invasion and ≤3 cm. Front Oncol, 12: 830470. [DOI:10.3389/fonc.2022.830470]
23. Ruan Z, Zhuo X, Xu C (2024) Diagnosis, treatment, and prognosis of stage IB non-small cell lung cancer with visceral pleural invasion. Front Oncol, 13: 1310471. [DOI:10.3389/fonc.2023.1310471]
24. Lin X, Liu K, Li K, et al. (2024) A CT-based deep learning model: visceral pleural invasion and survival prediction in clinical stage IA lung adenocarcinoma. iScience, 27(1): 108712. [DOI:10.1016/j.isci.2023.108712]
25. Choi H, Kim H, Hong W, et al. (2021) Prediction of visceral pleural invasion in lung cancer on CT: deep learning model achieves a radiologist-level performance with adaptive sensitivity and specificity to clinical needs. Eur Radiol, 31(5): 2866-2876. [DOI:10.1007/s00330-020-07431-2]
26. Kim H, Goo JM, Kim YT, et al. (2019) CT-defined visceral pleural invasion in T1 lung adenocarcinoma: lack of relationship to disease-free survival. Radiology, 293(3): 741-749. [DOI:10.1148/radiol.2019190297]
27. Kudo Y, Saito A, Horiuchi T, et al. (2025) Preoperative evaluation of visceral pleural invasion in peripheral lung cancer utilizing deep learning technology. Surg Today, 55(1): 18-28. [DOI:10.1007/s00595-024-02869-z]
28. Na HR, Moon SW, Kim KS, et al. (2024) Pleural carcinoembryonic antigen and maximum standardized uptake value as predictive indicators of visceral pleural invasion in clinical T1N0M0 lung adenocarcinoma. J Chest Surg, 57(1): 44-52. [DOI:10.5090/jcs.23.094]
29. Wang F, Pan X, Zhang T, et al. (2024) Predicting visceral pleural invasion in lung adenocarcinoma presenting as part-solid density utilizing a nomogram model combined with radiomics and clinical features. Thorac Cancer, 15(1): 23-34. [DOI:10.1111/1759-7714.15151]
30. Zha X, Liu Y, Ping X, et al. (2022) A nomogram combined radiomics and clinical features as imaging biomarkers for prediction of visceral pleural invasion in lung adenocarcinoma. Front Oncol, 12: 876264. [DOI:10.3389/fonc.2022.876264]
31. Wang Y, Lyu D, Fan L, et al. (2024) Research progress in predicting visceral pleural invasion of lung cancer: a narrative review. Transl Cancer Res, 13(1): 462-470. [DOI:10.21037/tcr-23-1318]
Wu L, Lin Q, Chen Y, Qiu N, Huang J. Immunohistochemical double staining with TTF-1 and aldehyde fuchsin with CT scan enhances the detection of visceral pleural invasion in lung cancer. Int J Radiat Res 2026; 24 (3) :805-812 URL: http://ijrr.com/article-1-7249-en.html