New immunohistochemical markers in the differential diagnosis of nonsmall cell lung carcinoma
New immunohistochemical markers in the differential diagnosis of nonsmall cell lung carcinoma
Background/aim: The aim of this study was to investigate Napsin-A, NTRK-1, NTRK-2, Desmoglein-3, and Desmocollin-3 in the differential diagnosis and prognosis of nonsmall cell lung cancer. Materials and methods: The expression of Napsin-A, NTRK-1, NTRK-2, and Desmoglein-3 was examined by immunohistochemistry in 50 squamous cell carcinomas and 50 adenocarcinomas. Desmocollin-3 was investigated in 29 squamous cell carcinoma and 29 adenocarcinoma cases. Associations between expression profiles of Napsin-A, NTRK-1, NTRK-2, Desmoglein-3, and Desmocollin-3 in lung cancers and clinicopathological variables were analyzed. Results: Napsin-A staining was statistically significant in detecting adenocarcinomas versus squamous cell carcinomas. The sensitivity of Napsin-A for adenocarcinomas was 96% and the specificity was 100%. NTRK-2 and Desmocollin-3 staining were statistically significant in detecting squamous cell carcinomas versus adenocarcinomas. Desmoglein-3, Napsin-A, and NTRK-2 had no effect on survival. Disease-free survival time was significantly shorter in cases that were moderately positive with NTRK-1. Conclusion: Our data suggest that Napsin-A, NTRK-2, and Desmocollin-3 are useful markers in the differentiation of nonsmall cell lung cancer.
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- 1. Siegel R, Naishadham D, Jemal A. Cancer statistics. CA Cancer J Clin 2012; 62: 10-29.
- 2. Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger K, Yatabe Y, Ishikawa Y, Wistuba I, Flieder DB, Franklin W et al. Diagnosis of lung cancer in small biopsies and cytology: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. Arch Pathol Lab Med 2013; 137: 668-684.
- 3. Savci-Heijink CD, Kosari F, Aubry MC, Caron BL, Sun Z, Yang P, Vasmatzis G. The role of Desmoglein-3 in the diagnosis of squamous cell carcinoma of the lung. Am J Pathol 2009; 174: 1629-1637.
- 4. Raparia K, Villa C, De Camp MM, Patel JD, Mehta MP. Molecular profiling in non-small cell lung cancer: a step toward personalized medicine. Arch Pathol Lab Med 2013; 137: 481- 491.
- 5. Jung CY. Biopsy and mutation detection strategies in nonsmall cell lung cancer. Tuberc Respir Dis (Seoul) 2013; 75: 181- 187.
- 6. Terry J, Leung S, Laskin J, Leslie KO, Gown AM, Ionescu DN. Optimal immunohistochemical markers for distinguishing lung adenocarcinomas from squamous cell carcinomas in small tumor samples. Am J SurgPathol 2010; 34: 1805-1811.
- 7. Camilo R, Capelozzi VL, Siqueira SA, Del Carlo Bernardi F. Expression of p63, keratin 5/6, keratin 7, and surfactant-A in non-small cell lung carcinomas. Hum Pathol 2006; 37: 542- 546.
- 8. Bishop JA, Sharma R, Illei PB. Napsin-A and thyroid transcription factor-1 expression in carcinomas of the lung, breast, pancreas, colon, kidney, thyroid, and malignant mesothelioma. Hum Pathol 2010; 41: 20-25.
- 9. Mori K, Shimizu H, Konno A, Iwanaga T. Immunohistochemical localization of napsin and its potential role in protein catabolism in renal proximal tubules. Arch Histol Cytol 2002; 65: 359-368.
- 10. Terry J, De Luca A, Leung S, Peacock G, Wang Y, Elliot WM, Huntsman D. Immunohistochemical expression of neurotrophic tyrosine kinase receptors 1 and 2 in lung carcinoma: potential discriminators between squamous and nonsquamous subtypes. Arch Pathol Lab Med 2011; 135: 433- 439.
- 11. Monica V, Ceppi P, Righi L, Tavaglione V, Volante M, Pelosi G, Scagliotti GV, Papotti M. Desmocollin-3: a new marker of squamous differentiation in undifferentiated large-cell carcinoma of the lung. Mod Pathol 2009; 22: 709-717.
- 12. Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger K, Yatabe Y, Ishikawa Y, Wistuba I, Flieder DB, Franklin W et al. Diagnosis of lung adenocarcinoma in resected specimens: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. Arch Pathol Lab Med 2013; 137: 685-705.
- 13. Rami-Porta R, Crowley J, Goldstraw P. The revised TNM staging system for lung cancer. Ann Thorac Cardiovasc Surg 2009; 15: 81-89.
- 14. Detterbeck FC, Boffa DJ, Tanoue T. The new lung cancer staging system. Chest 2009; 136: 260-271.
- 15. Hirano T, Auer G, Maeda M, Hagiwara Y, Okada S, Ohira T, Okuzawa K, Fujioka K, Franzén B, Hibi N et al. Human tissue distribution of TA02, which is homologous with a new type of aspartic proteinase, Napsin-A. Jpn J Cancer Res 2000; 91: 1015- 1021.
- 16. Hirano T, Gong Y, Yoshida K, Kato Y, Yashimara K, Maeda M, Nakagawa A, Fujioka K, Ohira T, Ikeda N et al. Usefulness of TA02 (Napsin-A) to distinguish primary lung adenocarcinoma from metastatic lung adenocarcinoma. Lung Cancer 2003; 41: 155-162.
- 17. Ordóñez NG. Napsin-A expression in lung and kidney neoplasia: a review and update. Adv Anat Pathol 2012; 19: 66- 73.
- 18. Ueno T, Linder S, Elmberger G. Aspartic proteinase Napsin-A is a useful marker for diagnosis of primary lung adenocarcinoma. Br J Cancer 2003; 88: 1229-1233.
- 19. Suzuki A, Shijubo N, Yamada G, Ichimiya S, Satoh M, Abe S, Sayo N. Napsin-A is useful to distinguish primary lung adenocarcinoma from adenocarcinomas of other organs. Pathol Res Pract 2005; 201: 579-586.
- 20. Stoll LM, Johnson MW, Gabrielson E, Askin F, Clark DP, Li QK. The utility of napsin-A in the identification of primary and metastatic lung adenocarcinoma among cytologically poorly differentiated carcinomas. Cancer Cytopathol 2010; 118: 441- 449.
- 21. Kadivar M, Boozari B. Applications and limitations of immunohistochemical expression of Napsin-A in distinguishing lung adenocarcinoma from adenocarcinomas of other organs. Appl Immunohistochem Mol Morphol 2013; 21: 191-195.
- 22. Yang M, Nonaka D. A study of immunohistochemical differential expression in pulmonary and mammary carcinomas. Mod Pathol 2010; 23: 654-661.
- 23. Mukhopadhyay S, Katzenstein AL. Subclassification of nonsmall cell lung carcinomas lacking morphologic differentiation on biopsy specimens: utility of an immunohistochemical panel containing TTF-1, Napsin-A, p63, and CK5/6. Am J Surg Pathol 2011; 35: 15-25.
- 24. Zhang S, Guo D, Luo W, Zhang Q, Zhang Y, Li C, Lu Y, Cui Z, Qiu X. TrkB is highly expressed in NSCLC and mediates BDNF-induced the activation of Pyk2 signaling and the invasion of A549 cells. BMC Cancer 2010; 10: 43.
- 25. Tsuta K, Tanabe Y, Yoshida A, Takahashi F, Maeshima AM, Asamura H, Tsuda H. 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: 1190-1199.
- 26. Fukuoka J, Dracheva T, Shih JH, Hewitt SM, Fujii T, Kishor A, Mann F, Shilo K, Franks TJ, Travis WD et al. Desmoglein 3 as a prognostic factor in lung cancer. Hum Pathol 2007; 38: 276- 283.
- 27. Cui T, Chen Y, Yang L, Knösel T, Zöller K, Huber O, Petersen I. DSC3 expression is regulated by p53, and methylation of DSC3 DNA is a prognostic marker in human colorectal cancer. Br J Cancer 2011; 104: 2326-2333.
- 28. Lee JG, Kim S, Shim HS. Napsin-A is an independent prognostic factor in surgically resected adenocarcinoma of the lung. Lung Cancer 2012; 77: 156-161.