Dergiler / Düzce Tıp Fakültesi Dergisi / 2026 / Volume: 28 Issue: 2

p53-Mutant Biphenotypic Non-Small Cell Lung Carcinoma with Coexpression of TTF-1 and p40: A Distinct Histopathologic Entity? A Case Report and Literature Review

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Yayın Tarihi
2026-08-21
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⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

Here, we present a rare case of TP53-mutant NSCLC exhibiting coexpression of TTF-1 and p40.

📌 3 Maddede Bu Makale

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Amaç & Hipotez:In non-small cell lung carcinoma (NSCLC), TTF-1 and p40 are well-established immunohistochemical markers for the separation of adenocarcinoma from squamous cell carcinoma.
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Temel Bulgular & Veri:These markers typically occur in distinct and separate tumor types; however, TTF-1 and p40 coexpression has been increasingly documented in recent years.
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Sonuç & Katkı:Here, we present a rare case of TP53-mutant NSCLC exhibiting coexpression of TTF-1 and p40.
🔬Tür:Case Report
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Non-small-cell lung carcinoma · thyroid transcription factor-1 · tumor suppressor protein p53

Abstract

In non-small cell lung carcinoma (NSCLC), TTF-1 and p40 are well-established immunohistochemical markers for the separation of adenocarcinoma from squamous cell carcinoma. These markers typically occur in distinct and separate tumor types; however, TTF-1 and p40 coexpression has been increasingly documented in recent years. Such tumors usually exhibit a basaloid cellular architecture, with the same neoplastic cells showing diffuse nuclear positivity for both markers. Molecular studies often detect mutations in TP53 as the main alteration in these tumors. Several reported cases have demonstrated aggressive behavior and have been associated with poor outcomes. The coexpression of TTF-1 and p40 may reflect a dual cell differentiation process driven by alterations in the p53 signaling pathway. Recent studies suggest that these tumors represent a distinct subtype of NSCLC within the current WHO and IASLC classification systems. Here, we present a rare case of TP53-mutant NSCLC exhibiting coexpression of TTF-1 and p40.

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Bu Makaleye Atıf Yap

Korkmaz, Ö. K., Türk, N., Karakulak, M. B. (2026). p53-Mutant Biphenotypic Non-Small Cell Lung Carcinoma with Coexpression of TTF-1 and p40: A Distinct Histopathologic Entity? A Case Report and Literature Review. Düzce Tıp Fakültesi Dergisi, Volume: 28 Issue: 2. https://doi.org/10.18678/dtfd.1882326

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Kaynakça (16)

  1. WHO Classification of Tumours Editorial Board. WHO Classification of Tumours: Thoracic Tumours. 5th ed. Lyon: International Agency for Research on Cancer; 2021.
  2. Affandi KA, Tizen NMS, Mustangin M, Zin RRMRM. p40 immunohistochemistry is an excellent marker in primary lung squamous cell carcinoma. J Pathol Transl Med. 2018;52(5):283-9. doi:10.4132/jptm.2018.08.14.
  3. Tsuta K, Tanabe Y, Yoshida A, Takahashi F, Maeshima AM, Asamura H, et al. Utility of 10 immunohistochemical markers including novel markers (desmocollin-3, glypican 3, S100A2, S100A7, and Sox-2) for differential diagnosis of squamous cell carcinoma from adenocarcinoma of the lung. J Thorac Oncol. 2011;6(7):1190-9. doi:10.1097/JTO.0b013e318219ac78.
  4. Pelosi G, Fabbri A, Bianchi F, Maisonneuve P, Rossi G, Barbareschi M, et al. ΔNp63 (p40) and thyroid transcription factor-1 immunoreactivity on small biopsies or cellblocks for typing non-small cell lung cancer: a novel two-hit, sparing-material approach. J Thorac Oncol. 2012;7(2):281-90. doi:10.1097/JTO.0b013e31823815d3.
  5. Pelosi G, Bulloni M, Vescio M, Uccella S, Forest F, Leone G, et al. Coexpression of ΔNp63/p40 and TTF1 within most of the same individual cells identifies life-threatening NSCLC featuring squamous and glandular biphenotypic differentiation: clinicopathologic correlations. JTO Clin Res Rep. 2021;2(11):100222. doi:10.1016/j.jtocrr.2021.100222.
  6. Terada K, Menju T, Date H, Haga H, Yoshizawa A. Non-small cell lung carcinoma with focal coexpression of thyroid transcription factor-1 and ΔNp63/p40: a case report. Thorac Cancer. 2024;15(12):1029-33. doi:10.1111/1759-7714.15271.
  7. Marando A, Zagni M, Negrelli M, Valtorta E, Lauricella C, Motta V, et al. Biphenotypic lung carcinoma with coexpression of TTF-1 and ΔNp63/p40 within most of the same individual cells: a further case confirming poor prognosis and a review of literature. Pathologica. 2024;116(1):13-21. doi:10.32074/1591-951X-957.
  8. Zhao Y, Wu D, Xiang X, Zhang B, Zhou N, Hu Y. p53 gene mutations in non-small cell lung cancer detected by polymerase chain reaction single-strand conformation polymorphism analysis. Chin Med Sci J. 1999;14(3):134-7.
  9. Sanchez-Vega F, Mina M, Armenia J, Chatila WK, Luna A, La KC, et al. Oncogenic signaling pathways in The Cancer Genome Atlas. Cell. 2018;173(2):321-37.e10. doi:10.1016/j.cell.2018.03.035.
  10. Garrido-Jimenez S, Barrera-Lopez JF, Diaz-Chamorro S, Mateos-Quiros CM, Rodriguez-Blanco I, Marquez-Perez FL, et al. p53 regulation by MDM2 contributes to self-renewal and differentiation of basal stem cells in mouse and human airway epithelium. FASEB J. 2021;35(9):e21816. doi:10.1096/fj.202100638R.
  11. Hayashi T, Takamochi K, Yanai Y, Mitani K, Tomita H, Mogushi K, et al. Non-small cell lung carcinoma with diffuse coexpression of thyroid transcription factor-1 and ΔNp63/p40. Hum Pathol. 2018;78:177-81. doi:10.1016/j.humpath.2018.01.023.
  12. Sun J, Shi H, Sun B, Wei T, Su J, Liu H, et al. TTF-1 and p40 co-expressing non-small cell lung cancer with ERBB2 and TP53 gene mutations: a case report and review of the literature. Medicine (Baltimore). 2025;104(6):e41290. doi:10.1097/MD.0000000000041290.
  13. Braun M, Sołek J, Stępień GJ, Masłowska AI, Kamecki M, Antosik P, et al. TTF-1 and p40 co-expression defines a distinct subtype of non-small cell lung cancer with frequent TP53 mutations and FGFR pathway dysregulation. Transl Lung Cancer Res. 2025;14(9):3988-4001. doi:10.21037/tlcr-2025-690.
  14. Mendoza RP, Chen-Yost HI, Wanjari P, Wang P, Symes E, Johnson DN, et al. Lung adenocarcinomas with isolated TP53 mutation: a comprehensive clinical, cytopathologic and molecular characterization. Cancer Med. 2024;13(1):e6873. doi:10.1002/cam4.6873.
  15. Wei C, Wang Y, Lu W, Lin BY, Gan D, Lu Y. Non-small cell lung carcinoma with co-expression of thyroid transcription factor-1 and p40: a case report and literature review. World J Surg Oncol. 2025;23(1):441. doi:10.1186/s12957-025-04103-7.
  16. Guo X, Dong L, Liu H, Chen X. TP53, NOTCH2, and STK11 mutations in a rare tumor of non-small cell lung carcinoma with diffuse coexpression of TTF1 and p40 in the same tumor cells. Int J Surg Pathol. 2023;31(6):1041-7. doi:10.1177/10668969221126105.