The diagnostic value of TTF1, P63, HMWK [34βE12], CK7, and CD56 immunostaining in classification of lung carcinoma

Document Type: Original Research


Dept. of Pathology, Faculty of Medicine, Mashhad University of Medical Sciences, Iran


Background & objective: The histologic distinction of small cell from non-small cell lung carcinoma and correct identification of all subtypes of lung carcinoma are very important in treatment management. The main method for histologic classification of lung tumors is based on morphology. However, in small bronchoscopic biopsies in particular, distinction is very difficult upon morphology alone. The current study aimed at evaluating the utility of a panel of antibodies, consisting of thyroid transcription factor (TTF-1), P63, high molecular weight keratin [HMWK (34βE12)], cytokeratin (CK7), and cluster of differentiation (CD56) for accurate distinction of bronchogenic carcinomas.
Methods: Bronchoscopic biopsies of 60 lung carcinoma cases including 20 small cell carcinomas, 20 adenocarcinomas, and 20 squamous cell carcinomas (SCCs) with typical morphologic features were selected. All these cases were immunohistochemically stained for TTF-1, P63, HMWK (34βE12), CK7, and CD56. All immunostained slides were scored as either positive or negative.
Results: The mean age of the patients was 60 years; ranged from 35 to 81. Sixteen patients were female and 44 were male. All adenocarcinomas were positive for CK7 and most of them (18/20; 90%) were positive for TTF-1. Most of small cell lung carcinomas were positive for TTF-1 (17/20; 85%), and CD56 (18/20; 90%). All squamous cell carcinomas (SCCs) were negative for TTF-1, but most of them were positive for HMWK (34βE12) and P63.
Conclusion: The obtained data showed that TTF-1, P63, CK7, CD56 and/or 34βE12 represent a useful panel of antibodies to identify lung carcinoma subtypes in small bronchoscopic biopsies.


Forman D, Ferlay J, Stewart B, Wild C. The global and regional burden of cancer. World cancer report. 2014:16-53.

2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA: a cancer journal for clinicians. 2016; 66 (1):7-30.

3. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA: a cancer journal for clinicians. 2013;63 (1):11-30.

4. Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG. Introduction to the 2015 World Health Organization Classification of Tumors of the Lung, Pleura, Thymus, and Heart. Journal of Thoracic Oncology. 2015; 10 (9):1240-2.

5. Kargi A, Gurel D, Tuna B. The diagnostic value of TTF-1, CK 5/6, and p63 immunostaining in classification of lung carcinomas. Applied Immunohistochemistry & Molecular Morphology. 2007;15(4):415-20.

6. Au N, Gown A, Cheang M, Huntsman D, Yorida E, Elliott W, et al. P63 expression in lung carcinoma: a tissue microarray study of 408 cases. Applied Immunohistochemistry & Molecular Morphology. 2004;12(3):240-7.

7. Wang BY, Gil J, Kaufman D, Gan L, Kohtz DS, Burstein DE. P63 in pulmonary epithelium, pulmonary squamous neoplasms, and other pulmonary tumors. Human pathology. 2002;33 (9):921-6.

8. Jerome Marson V, Mazieres J, Groussard O, Garcia O, Berjaud J, Dahan M, et al. Expression of TTF‐1 and cytokeratins in primary and secondary epithelial lung tumours: correlation with histological type and grade. Histopathology. 2004;45(2):125-34.


9. Johansson L. Histopathologic classification of lung cancer: relevance of cytokeratin and TTF-1 immunophenotyping. Annals of diagnostic pathology. 2004;8(5):259-67.

10. Lyda MH, Weiss LM. Immunoreactivity for epithelial and neuroendocrine antibodies are useful in the differential diagnosis of lung carcinomas. Human pathology. 2000;31(8):980-7.


11. Rossi G, Marchioni A, Milani M, Scotti R, Foroni M, Cesinaro A, et al. TTF-1, cytokeratin 7, 34βE12, and CD56/NCAM immunostaining in the subclassification of large cell carcinomas of the lung. American journal of clinical pathology. 2004;122(6):884-93.

12. Sturm N, Lantuéjoul S, Laverrière M-H, Papotti M, Brichon P-Y, Brambilla C, et al. Thyroid transcription factor 1 and cytokeratins 1, 5, 10, 14 (34βE12) expression in basaloid and large-cell neuroendocrine carcinomas of the lung. Human pathology. 2001;32(9):918-25.

13. Viberti L, Bongiovanni M, Croce S, Bussolati G. 34βE 12 Cytokeratin Immunodetection in the Differential Diagnosis of Small Cell Tumors of Lung. International journal of surgical pathology. 2000;8(4):317-22.

14. Al-Zahrani IH. The value of immunohistochemical expression of TTF-1, CK7 and CK20 in the diagnosis of primary and secondary lung carcinomas. Saudi medical journal. 2008;29(7):957-61.

15. Ionescu DN, Treaba D, Gilks CB, Leung S, Renouf D, Laskin J, et al. Nonsmall cell lung carcinoma with neuroendocrine differentiation—an entity of no clinical or prognostic significance. The American journal of surgical pathology. 2007;31(1):26-32.