Skip Navigation LinksHome > January 2012 - Volume 19 - Issue 1 > Napsin A Expression in Lung and Kidney Neoplasia: A Review...
Advances in Anatomic Pathology:
doi: 10.1097/PAP.0b013e31823e472e
New Antibody/Techniques

Napsin A Expression in Lung and Kidney Neoplasia: A Review and Update

Ordóñez, Nelson G. MD

Free Access
Article Outline
Collapse Box

Author Information

University of Texas, M.D. Anderson Cancer Center, Houston, TX

The author has no funding or conflicts of interest to disclose.

Reprints: Nelson G. Ordóñez, MD, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030 (e-mail:

Collapse Box


Napsin A is an aspartic protease present in the epithelial cells of the lung and kidney. Recent studies have shown that, in lung tumors, napsin A expression is restricted to lung adenocarcinomas, whereas among renal tumors, it is frequently expressed in renal cell carcinomas, especially the papillary and clear cell subtypes. Owing to its restricted expression, napsin A is a useful marker that can assist in the diagnosis of both lung adenocarcinomas and renal cell carcinomas.

Until recently, surfactant proteins, especially surfactant protein A (SP-A) and thyroid transcription factor-1 (TTF-1), were the only peripheral airway epithelial cell markers recognized as being useful in the diagnosis of lung adenocarcinomas. SP-A, although highly specific for lung adenocarcinoma, has a relatively low sensitivity when compared with TTF-1.1,2 It also has the drawback of its expression being directly related to histologic subtype and degree of differentiation.3–5 Although well-differentiated adenocarcinomas usually strongly express SP-A, poorly differentiated tumors, which are often the ones that pose the most diagnostic difficulty, are usually negative.6 As a result of this, over the past decade, TTF-1 became the lung-associated marker used more often by surgical pathologists to assist in the diagnosis and classification of lung tumors. Among lung carcinomas, TTF-1 is expressed in 75% to 85% of adenocarcinomas.7–12 It is not related to histologic subtype as acinar, tubular, bronchioloalveolar, mucinous (colloid), and signet-ring cell adenocarcinomas can express this antigen.13–15 Among neuroendocrine carcinomas of the lung, the vast majority of small cell carcinomas exhibit reactivity for TTF-1 (80% to 90%),16–18 whereas typical and atypical carcinoid tumors and poorly differentiated non-small cell neuroendocrine carcinomas exhibit a lower percentage of positivity. Only a minority of sarcomatoid carcinomas have been reported to be TTF-1 positive.19–21 Squamous cell carcinomas are commonly negative; however, a percentage of positive cases (1% to 37%) have been reported in some series.1,14,17,22–32 Despite its high specificity for tumors of thyroid and lung origin, TTF-1 is not absolutely specific as it can frequently be demonstrated in some extrapulmonary small cell carcinomas16,33–35 and, on rare occasions, in adenocarcinomas of the colon,12,30,36,37 stomach,7,30,38 ovary,17,39,40 endometrium,7,40–42 uterine cervix,41,43 and breast.44

With the introduction of newer biologically targeted chemotherapy, an accurate classification of lung tumors has become increasingly important. It has recently been reported that napsin A is both a more sensitive marker for lung adenocarcinomas than SP-A and a more specific marker than TTF-1, and that, because of this, immunostaining for napsin A could be very valuable in assisting in the differential diagnosis of these tumors.

Napsin A, also known as aspartyl protease 4, ASP4, napsin 1, TA01/TA02, Kdap, SNAPA, and EC3.4.23, is an aspartic proteinase that belongs to the peptidase A1 family, which also includes cathepsins D and E, renin, pepsin, gastricsin, and bovine chymosin. It is a single chain protein of 420 amino acids with a molecular weight of approximately 45 kDa that is encoded by the NSPSA gene located on chromosome 19q13.3.45,46 Napsin A is predominantly expressed in the lung and kidney.47–50 It has been demonstrated that the expression of napsin A is regulated by TTF-1, which also regulates the expression of surfactant protein B.51 In the lung, napsin A is expressed in alveolar type II pneumocytes, where by immunoelectron microscopy it has been demonstrated to be colocalized with prosurfactant B protein and surfactant B in the lamellar bodies, and it is believed to be involved in the N-terminal and C-terminal processing of prosurfactant B protein.52,53 Napsin A is also present in intra-alveolar macrophages, presumably as a result of phagocytosis (Fig. 1A). In the kidney, napsin A is expressed in the proximal tubules, where it is believed to function as a lysosomal protease involved in protein catabolism54 (Fig. 1B).

Figure 1
Figure 1
Image Tools
Back to Top | Article Outline


Immunohistochemical studies have shown that the napsin A staining pattern in lung adenocarcinomas is granular and cytoplasmic (Fig. 1C). The first investigation into the expression of this marker in lung carcinomas was by Hirano et al49 in 2000. Using the 4B2 anti-napsin A mouse monoclonal antibody, these authors reported napsin A positivity in 47 (81%) of 58 adenocarcinomas, but in none of the squamous cell carcinomas, small cell carcinomas, or carcinoid tumors included in the study. In a subsequent study by the same group of investigators published in 2003 in which the TMU-Ad02 mouse monoclonal antibody was used napsin A positivity was demonstrated in 39 (91%) of 43 lung adenocarcinomas, whereas all of the squamous cell carcinomas, small cell carcinomas, and carcinoid tumors were negative for this marker.55 Subsequent studies by other groups of investigators using the TMU-Ad02, IP64, or KCG1.1 monoclonal antibodies have reported comparable results with those obtained by Hirano et al55 (Table 1). The percentage of napsin A positivity in adenocarcinomas in different published studies has ranged from 58% up to 91% of the cases.1,2,6,49,55–58 It should be pointed out that the lower percentages reported were in studies using either tissue microarray,59 biopsy specimens,62 or cytology material31 (Table 1). Several comparative studies on napsin A and TTF-1 expression have been published, some of which have indicated that napsin A is a more sensitive marker for lung adenocarcinomas than TTF-1,37,56,58,61 whereas others have shown the opposite2,31,59,60,62 (Table 2). In a combined review of 11 such studies, 627 (75%) of 836 lung adenocarcinomas were reported to be napsin A positive, whereas 623 (74.4%) of 837 exhibited TTF-1 positivity.1,2,31,32,37,56,58–62 These results indicate that the sensitivity of napsin A for lung adenocarcinomas is comparable with that of TTF-1. Only 1 investigation has been published on the expression of napsin A in bronchioloalveolar adenocarcinomas.31 The results of that study indicate that, similar to TTF-1, napsin A is expressed in the majority of cases of both mucinous and nonmucinous tumors, but its sensitivity is higher than that of TTF-1. All 7 of the adenocarcinomas with enteric differentiation investigated for napsin A expression by Inamura et al2 were negative for this marker, whereas 3 (43%) of the 7 were positive for TTF-1.

Table 1
Table 1
Image Tools
Table 2
Table 2
Image Tools

None of the small cell carcinomas or carcinoid tumors of the lung that have been investigated for napsin A expression have been shown to express this marker.6,31,53,58 This is in contrast to TTF-1, which has been reported to be expressed in the large majority of small cell carcinomas (80% to 100%)16,33,65–68 and in a large percentage (35% to 70%) of carcinoid tumors of the lung.65,69–71 It should be emphasized, however, that the number of cases of neuroendocrine carcinomas of the lung that have been investigated for napsin A expression is too low to draw any definitive conclusion regarding the expression of this marker in these tumors (Table 1).

The majority of published studies have indicated that napsin A is not expressed in squamous carcinomas of the lung1,6,31,58,60,62; however, 2 of the most recent publications on napsin A expression in these tumors have reported positivity in 12.5% and 26% of the cases, respectively.32,64 In a recent study by this investigator, none of the 70 pulmonary or 32 extrapulmonary squamous cell carcinomas investigated exhibited napsin A expression.72 As intra-alveolar macrophages and hyperplastic type II pneumocytes show strong napsin A positivity (Fig. 1D), it was suggested that these cells were the most likely cause of the napsin A positivity reported in the 2 previously mentioned investigations, particularly when it is considered that one of the studies was done on sections of cell blocks prepared from fine needle aspiration biopsies and the other on tissue microarrays in which it can sometimes be difficult to determine whether the reactive cells are tumors cells or, in actuality, represent non-neoplastic entrapped cells within the tumor.

Back to Top | Article Outline


In 2003, using in situ hybridization, Ueno et al1 were the first to report napsin A expression in a renal cell carcinoma. Subsequent immunohistochemical studies have demonstrated napsin A positivity in the majority of papillary renal cell carcinomas (75% to 83%),31,37,58,73 in a smaller percentage (10% to 43%) of clear cell renal cell carcinomas,31,37,58,73 and rarely (3%) in chromophobe renal cell carcinomas58 (Table 3). In a combined review of 4 published series, 54 (79%) of 68 papillary and 21 (28%) of 76 clear cell carcinomas exhibited expression for this marker.31,37,58,73 Although none of the Xp11 translocation renal cell carcinomas or renal oncocytomas that have been investigated has shown napsin A positivity, relatively few such cases have been included in published series; therefore, no definitive conclusions regarding the expression of this marker in these types of tumors can be drawn. Examples of papillary and clear cell renal cell carcinomas exhibiting napsin A positivity are shown in Figures 1E and F

Table 3
Table 3
Image Tools
Back to Top | Article Outline


It has become increasingly important to distinguish between adenocarcinomas and squamous cell carcinomas of the lung because of the development of targeted therapies, as these new therapies may have different therapeutic or adverse effects, depending on the histologic type of the tumor. Although the differential diagnosis between adenocarcinomas and squamous cell carcinomas is relatively easy on hematoxylin-and-eosin-stained sections when the tumors are rather well differentiated, when they are poorly differentiated, their distinction can be difficult, especially in small biopsy specimens. The differential diagnosis, however, can be greatly facilitated by the use of napsin A immunostaining, combined with other markers, such as TTF-1, keratin 5/6, p63, and keratin 7. TTF-1 is a marker that, in my experience,74 and that of other investigators,8,33,58,60,62,68 is not expressed in squamous cell carcinomas of the lung and it has been reported to react in some of the lung adenocarcinomas that do not express napsin A. Keratin 5/6 is a highly specific squamous cell carcinoma marker that is usually absent in lung adenocarcinomas. p63 and keratin 7 are highly sensitive markers for squamous cell carcinomas and lung adenocarcinomas, respectively, although p63 has been reported in 15% up to 65% of lung adenocarcinomas75–78 and keratin 7 in 20% to 60% of squamous cell carcinomas.28,74,78–82 These findings indicate that the specificity of these 2 markers is lower than that of TTF-1, napsin A, and keratin 5/6.

Epithelioid mesotheliomas can potentially be confused with a lung adenocarcinoma involving the pleura. Several immunohistochemical studies, however, have shown that because napsin A is frequently expressed in lung adenocarcinomas, but absent in mesotheliomas, immunostaining for this marker can assist in discriminating between these 2 malignancies.55–58 Therefore, napsin A should be included in the panel of immunohistochemical markers used to assess pleural-based malignancies.11,83

Renal cell carcinomas, particularly papillary and clear cell renal cell carcinomas, have been shown to express napsin A31,37,58,73; therefore, immunostaining for this marker may have some utility in assisting in the diagnosis of these tumors. Compared with Pax-8, which is also a novel marker for renal cell carcinomas, napsin A seems to be less sensitive, but more specific.84 In contrast to Pax-8, which has been reported to be frequently expressed in other tumors, especially in thyroid carcinomas,84–87 ovarian, endometrial, and cervical adenocarcinomas,84,88,89 thymic epithelial tumors,84 and neuroendocrine carcinomas of the pancreas and gastrointestinal tract,90,91 napsin A is largely restricted to lung adenocarcinomas and renal cell carcinomas.

As the histologic features of adenocarcinomas of different sites overlap, the diagnosis of these tumors, when they present as a metastasis of unknown origin, can be difficult. Primary lung adenocarcinomas can be difficult to distinguish from metastatic adenocarcinomas arising from various sites, particularly when they present as a solitary lung lesion in a patient who has no known history of a malignant condition. Current information indicates that napsin A is almost exclusively expressed in lung adenocarcinomas and papillary and clear cell renal cell carcinomas. Only 2 of 53 thyroid carcinomas in 1 study were reported to be napsin A positive.58 None of the 329 carcinomas of other sites, including the breast, colon, stomach, pancreas, liver, ovary, or endometrium, that were investigated for napsin A expression in several studies were positive for this marker.2,6,31,37,55,56,58,60,61 These findings indicate that napsin A could be a very useful marker in the study of metastatic adenocarcinomas of unknown primary site, especially when it is used in conjunction with other organ-related markers.

Back to Top | Article Outline


At present, 3 anti-napsin A mouse monoclonal antibodies (clones TMU-Ad02, IP64, and KCG1.1) and a few rabbit polyclonal antibodies that can be used on formalin-fixed, paraffin-embedded tissue specimens are commercially available. As the TMU-Ad02 clone was the first to become available, it is also the one that has been the most frequently used in published studies.2,6,55–57,60,62 This antibody, also known as 6A1, was developed by Hirano et al49 in 2000 using a 33 amino acid N-terminal sequence as immunogen. The IP64 antibody was generated using a recombinant protein corresponding to a 126 amino acid region of napsin A and the KCG1.1 antibody was, according to the commercial source, produced using a synthetic peptide corresponding to the N-terminal of the napsin A protein. Both of the latter antibodies have been used in more recent published studies.31,32,37,58,61 Although no comparative studies using the 3 previously mentioned anti-napsin A mouse monoclonal antibodies have been published, current information indicates that they have a comparable sensitivity and specificity for lung adenocarcinomas (Table 1). There are no publications utilizing the commercially available polyclonal antibodies.

Back to Top | Article Outline


1. Ueno T, Linder S, Elmberger G. Aspartic proteinase napsin is a useful marker for diagnosis of primary lung adenocarcinoma. Br J Cancer. 2003;88:1229–1233

2. Inamura K, Satoh Y, Okumura S, et al. Pulmonary adenocarcinomas with enteric differentiation: histologic and immunohistochemical characteristics compared with metastatic colorectal cancers and usual pulmonary adenocarcinomas. Am J Surg Pathol. 2005;29:660–665

3. Mizutani Y, Nakajima T, Morinaga S, et al. Immunohistochemical localization of pulmonary surfactant apoproteins in various lung tumors. Special reference to nonmucus producing lung adenocarcinomas. Cancer. 1988;61:532–537

4. Noguchi M, Nakajima T, Hirohashi S, et al. Immunohistochemical distinction of malignant mesothelioma from pulmonary adenocarcinoma with anti-surfactant apoprotein, anti-Lewisa, and anti-Tn antibodies. Hum Pathol. 1989;20:53–57

5. Nicholson AG, McCormick CJ, Shimosato Y, et al. The value of PE-10, a monoclonal antibody against pulmonary surfactant, in distinguishing primary and metastatic lung tumours. Histopathology. 1995;27:57–60

6. Suzuki A, Shijubo N, Yamada G, et al. Napsin is useful to distinguish primary lung adenocarcinoma from adenocarcinomas of other organs. Pathol Res Pract. 2005;201:579–586

7. Bejarano PA, Baughman RP, Biddinger PW, et al. Surfactant proteins and thyroid transcription factor-1 in pulmonary and breast carcinomas. Mod Pathol. 1996;9:445–452

8. Khoor A, Whitsett JA, Stahlman MT, et al. Utility of surfactant protein B precursor and thyroid transcription factor 1 in differentiating adenocarcinoma of the lung from malignant mesothelioma. Hum Pathol. 1999;30:695–700

9. Ordóñez NG. Value of thyroid transcription factor-1, E-cadherin, BG8, WT1, and CD44S immunostaining in distinguishing epithelial pleural mesothelioma from pulmonary and nonpulmonary adenocarcinoma. Am J Surg Pathol. 2000;24:598–606

10. Barbareschi M, Murer B, Colby TV, et al. CDX-2 homeobox gene expression is a reliable marker of colorectal adenocarcinoma metastases to the lungs. Am J Surg Pathol. 2003;27:141–149

11. Ordóñez NG. Application of mesothelin immunostaining in tumor diagnosis. Am J Surg Pathol. 2003;27:1418–1428

12. Comperat E, Zhang F, Perrotin C, et al. Variable sensitivity and specificity of TTF-1 antibodies in lung metastatic adenocarcinoma of colorectal origin. Mod Pathol. 2005;18:1371–1376

13. Merchant SH, Amin MB, Tamboli P, et al. Primary signet-ring cell carcinoma of lung: immunohistochemical study and comparison with non-pulmonary signet-ring cell carcinomas. Am J Surg Pathol. 2001;25:1515–1519

14. Chang YL, Lee YC, Liao WY, et al. The utility and limitation of thyroid transcription factor-1 protein in primary and metastatic pulmonary neoplasms. Lung Cancer. 2004;44:149–157

15. Tsuta K, Ishii G, Nitadori J, et al. Comparison of the immunophenotypes of signet-ring cell carcinoma, solid adenocarcinoma with mucin production, and mucinous bronchioloalveolar carcinoma of the lung characterized by the presence of cytoplasmic mucin. J Pathol. 2006;209:78–87

16. Ordóñez NG. Value of thyroid transcription factor-1 immunostaining in distinguishing small cell lung carcinomas from other small cell carcinomas. Am J Surg Pathol. 2000;24:1217–1223

17. Zhang H, Liu J, Cagle PT, et al. Distinction of pulmonary small cell carcinoma from poorly differentiated squamous cell carcinoma: an immunohistochemical approach. Mod Pathol. 2005;18:111–118

18. Bobos M, Hytiroglu P, Kostopoulos I, et al. Immunohistochemical distinction between Merkel cell carcinoma and small cell carcinoma of the lung. Am J Dermatopathol. 2006;28:99–104

19. Rossi G, Cavazza A, Sturm N, et al. Pulmonary carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements: a clinicopathologic and immunohistochemical study of 75 cases. Am J Surg Pathol. 2003;27:311–324

20. Lewis JS, Ritter JH, El-Mofty S. Alternative epithelial markers in sarcomatoid carcinomas of the head and neck, lung, and bladder-p63, MOC-31, and TTF-1. Mod Pathol. 2005;18:1471–1481

21. Takeshima Y, Amatya VJ, Kushitani K, et al. Value of immunohistochemistry in the differential diagnosis of pleural sarcomatoid mesothelioma from lung sarcomatoid carcinoma. Histopathology. 2009;54:667–676

22. Fabbro D, Di Loreto C, Stamerra O, et al. TTF-1 gene expression in human lung tumours. Eur J Cancer. 1996;32A:512–517

23. Puglisi F, Barbone F, Damante G, et al. C. Prognostic value of thyroid transcription factor-1 in primary, resected, non-small cell lung carcinoma. Mod Pathol. 1999;12:318–324

24. Hecht JL, Pinkus JL, Weinstein LJ, et al. The value of thyroid transcription factor-1 in cytologic preparations as a marker for metastatic adenocarcinoma of lung origin. Am J Clin Pathol. 2001;116:483–488

25. Pelosi G, Fraggetta F, Pasini F, et al. Immunoreactivity for thyroid transcription factor-1 in stage I non-small cell carcinomas of the lung. Am J Surg Pathol. 2001;25:363–372

26. Haque AK, Syed S, Lele SM, et al. Immunohistochemical study of thyroid transcription factor-1 and HER2/neu in non-small cell lung cancer: strong thyroid transcription factor-1 expression predicts better survival. Appl Immunohist Mol Morphol. 2002;10:103–109

27. Tan D, Li Q, Deeb G, et al. Thyroid transcription factor-1 expression prevalence and its clinical implications in non-small cell lung cancer: a high-throughput tissue microarray and immunohistochemistry study. Hum Pathol. 2003;34:597–604

28. Jerome Marson V, Mazieres J, Groussard O, et al. Expression of TTF-1 and cytokeratins in primary and secondary epithelial lung tumours: correlation with histological type and grade. Histopathology. 2004;45:125–134

29. Wang LJ, Greaves WO, Sabo E, et al. GCDFP-15 positive and TTF-1 negative primary lung neoplasms: a tissue microarray study of 381 primary lung tumors. Appl Immunohistochem Mol Morphol. 2009;17:505–511

30. Matoso A, Singh K, Jacob R, et al. Comparison of thyroid transcription factor-1 expression by 2 monoclonal antibodies in pulmonary and nonpulmonary primary tumors. Appl Immunohistochem Mol Morphol. 2010;18:142–149

31. Stoll LM, Johnson MW, Gabrielson E, et al. 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

32. Fatima N, Cohen C, Lawson D, et al. TTF-1 and Napsin A double stain: a useful marker for diagnosing lung adenocarcinoma on fine-needle aspiration cell blocks. Cancer Cytopathol. 2011;119:127–133

33. Kaufmann O, Dietel M. Thyroid transcription factor-1 is the superior immunohistochemical marker for pulmonary adenocarcinomas and large cell carcinomas compared to surfactant proteins A and B. Histopathology. 2000;36:8–16

34. Cheuk W, Kwan MY, Suster S, et al. Immunostaining for thyroid transcription factor 1 and cytokeratin 20 aids the distinction of small cell carcinoma from Merkel cell carcinoma, but not pulmonary from extrapulmonary small cell carcinomas. Arch Pathol Lab Med. 2001;125:228–231

35. Yao JL, Madeb R, Bourne P, et al. Small cell carcinoma of the prostate: an immunohistochemical study. Am J Surg Pathol. 2006;30:705–712

36. Xu B, Thong N, Tan D, et al. Expression of thyroid transcription factor-1 in colorectal carcinoma. Appl Immunohistochem Mol Morphol. 2010;18:244–249

37. Ye J, Findeis-Hosey JJ, Yang Q, et al. Combination of Napsin A and TTF-1 immunohistochemistry helps in differentiating primary lung adenocarcinoma from metastatic carcinoma in the lung. Appl Immunohistochem Mol Morphol. 2011;19:313–317

38. Nakamura N, Miyagi E, Murata S, et al. Expression of thyroid transcription factor-1 in normal and neoplastic lung tissues. Mod Pathol. 2002;15:1058–1067

39. Kubba LA, McCluggage WG, Liu J, et al. Thyroid transcription factor-1 expression in ovarian epithelial neoplasms. Mod Pathol. 2008;21:485–490

40. Fujiwara S, Nawa A, Nakanishi T, et al. Thyroid transcription factor 1 expression in ovarian carcinomas is an independent prognostic factor. Hum Pathol. 2010;41:560–565

41. Siami K, McCluggage WG, Ordóñez NG, et al. Thyroid transcription factor-1 expression in endometrial and endocervical adenocarcinomas. Am J Surg Pathol. 2007;31:1759–1763

42. Zhang PJ, Gao HG, Pasha TL, et al. TTF-1 expression in ovarian and uterine epithelial neoplasia and its potential significance, an immunohistochemical assessment with multiple monoclonal antibodies and different secondary detection systems. Int J Gynecol Pathol. 2009;28:10–18

43. Han CP, Kok LF, Lee MY, et al. Five commonly used markers (p53, TTF1, CK7, CK20, and CK34betaE12) are of no use in distinguishing between primary endocervical and endometrial adenocarcinomas in a tissue microarray extension study. Arch Gynecol Obstet. 2010;281:317–323

44. Robens J, Goldstein L, Gown AM, et al. Thyroid transcription factor-1 expression in breast carcinomas. Am J Surg Pathol. 2010;34:1881–1885

45. Mori K, Ogawa Y, Tamura N, et al. Molecular cloning of a novel mouse aspartic protease-like protein that is expressed abundantly in the kidney. FEBS Lett. 1997;401:218–222

46. Tatnell PJ, Powell DJ, Hill J, et al. Napsins: new human aspartic proteinases. Distinction between two closely related genes. FEBS Lett. 1998;441:43–48

47. Chuman Y, Bergman A, Ueno T, et al. Napsin A, a member of the aspartic protease family, is abundantly expressed in normal lung and kidney tissue and is expressed in lung adenocarcinomas. FEBS Lett. 1999;462:129–134

48. Schauer-Vukasinovic V, Bur D, Kling D, et al. Human napsin A: expression, immunochemical detection, and tissue localization. FEBS Lett. 1999;462:135–139

49. Hirano T, Auer G, Maeda M, 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

50. Mori K, Kon Y, Konno A, et al. Cellular distribution of napsin (kidney-derived aspartic protease-like protein, KAP) mRNA in the kidney, lung and lymphatic organs of adult and developing mice. Arch Histol Cytol. 2001;64:319–327

51. De Felice M, Esposito L, Pucci B, et al. Biochemical characterization of a CDC6-like protein from the crenarchaeon Sulfolobus solfataricus. J Biol Chem. 2003;278:46424–46431

52. Brasch F, Ochs M, Kahne T, et al. Involvement of napsin A in the C- and N-terminal processing of surfactant protein B in type-II pneumocytes of the human lung. J Biol Chem. 2003;278:49006–49014

53. Ueno T, Linder S, Na CL, et al. Processing of pulmonary surfactant protein B by napsin and cathepsin H. J Biol Chem. 2004;279:16178–16184

54. Mori K, Shimizu H, Konno A, et al. Immunohistochemical localization of napsin and its potential role in protein catabolism in renal proximal tubules. Arch Histol Cytol. 2002;65:359–368

55. Hirano T, Gong Y, Yoshida K, et al. Usefulness of TA02 (napsin A) to distinguish primary lung adenocarcinoma from metastatic lung adenocarcinoma. Lung Cancer. 2003;41:155–162

56. Dejmek A, Naucler P, Smedjeback A, et al. Napsin A (TA02) is a useful alternative to thyroid transcription factor-1 (TTF-1) for the identification of pulmonary adenocarcinoma cells in pleural effusions. Diagn Cytopathol. 2007;35:493–497

57. Amatya VJ, Takeshima Y, Kohno H, et al. Caveolin-1 is a novel immunohistochemical marker to differentiate epithelioid mesothelioma from lung adenocarcinoma. Histopathology. 2009;55:10–19

58. Bishop JA, Sharma R, Illei PB, et al. 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

59. Terry J, Leung S, Laskin J, et al. Optimal immunohistochemical markers for distinguishing lung adenocarcinomas from squamous cell carcinomas in small tumor samples. Am J Surg Pathol. 2010;34:1805–1811

60. Yang M, Nonaka D. A study of immunohistochemical differential expression in pulmonary and mammary carcinomas. Mod Pathol. 2010;23:654–661

61. Kim JH, Kim YS, Choi YD, et al. Utility of napsin A and thyroid transcription factor 1 in differentiating metastatic pulmonary from non-pulmonary adenocarcinoma in pleural effusion. Acta Cytol. 2011;55:266–270

62. Mukhopadhyay S, Katzenstein AL. Subclassification of non-small 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

63. Hatanaka K, Tsuta K, Watanabe K, et al. Primary pulmonary adenocarcinoma with enteric differentiation resembling metastatic colorectal carcinoma: a report of the second case negative for cytokeratin 7. Pathol Res Pract. 2011;207:188–191

64. Pereira TC, Share SM, Magalhães AV, et al. Can we tell the site of origin of metastatic squamous cell carcinoma? An immunohistochemical tissue microarray study of 194 cases. Appl Immunohistochem Mol Morphol. 2011;19:10–14

65. Folpe AL, Gown AM, Lamps LW, et al. Thyroid transcription factor-1: immunohistochemical evaluation in pulmonary neuroendocrine tumors. Mod Pathol. 1999;12:5–8

66. Byrd-Gloster AL, Khoor A, Glass LF, et al. Differential expression of thyroid transcription factor 1 in small cell lung carcinoma and Merkel cell tumor. Hum Pathol. 2000;31:58–62

67. Wu M, Wang B, Gil J, et al. p63 and TTF-1 immunostaining. A useful marker panel for distinguishing small cell carcinoma of lung from poorly differentiated squamous cell carcinoma of lung. Am J Clin Pathol. 2003;119:696–702

68. Kargi A, Gurel D, Tuna B. The diagnostic value of TTF-1, CK 5/6, and p63 immunostaining in classification of lung carcinomas. Appl Immunohistochem Mol Morphol. 2007;15:415–420

69. Cai YC, Banner B, Glickman J, et al. Cytokeratin 7 and 20 and thyroid transcription factor 1 can help distinguish pulmonary from gastrointestinal carcinoid and pancreatic endocrine tumors. Hum Pathol. 2001;32:1087–1093

70. Lin X, Saad RS, Luckasevic TM, et al. Diagnostic value of CDX-2 and TTF-1 expressions in separating metastatic neuroendocrine neoplasms of unknown origin. Appl Immunohistochem Mol Morphol. 2007;15:407–414

71. Srivastava A, Hornick JL. Immunohistochemical staining for CDX-2, PDX-1, NESP-55, and TTF-1 can help distinguish gastrointestinal carcinoid tumors from pancreatic endocrine and pulmonary carcinoid tumors. Am J Surg Pathol. 2009;33:626–632

72. Ordóñez NG A word of caution regarding napsin A expression in squamous cell carcinomas of the lung. Am J Surg Pathol. (In press)

73. Argani P, Hicks J, De Marzo AM, et al. Xp11 translocation renal cell carcinoma (RCC): extended immunohistochemical profile emphasizing novel RCC markers. Am J Surg Pathol. 2010;34:1295–1303

74. Ordóñez NG. The diagnostic utility of immunohistochemistry in distinguishing between epithelioid mesotheliomas and squamous carcinomas of the lung: a comparative study. Mod Pathol. 2006;19:417–428

75. Kaufmann O, Fietze E, Mengs J, et al. Value of p63 and cytokeratin 5/6 as immunohistochemical markers for the differential diagnosis of poorly differentiated and undifferentiated carcinomas. Am J Clin Pathol. 2001;116:823–830

76. Wang BY, Gil J, Kaufman D, et al. p63 in pulmonary epithelium, pulmonary squamous neoplasms, and other pulmonary tumors. Hum Pathol. 2002;33:921–926

77. Au NHC, Gown AM, Cheang M, et al. p63 expression in lung carcinoma: A tissue microarray study of 408 cases. Appl Immunohistochem Mol Morphol. 2004;12:240–247

78. Ocque R, Tochigi N, Ohori NP, et al. Usefulness of immunohistochemical and histochemical studies in the classification of lung adenocarcinoma and squamous cell carcinoma in cytologic specimens. Am J Clin Pathol. 2011;136:81–87

79. Nhung NV, Mirejovsky P, Mirejovsky T, et al. Cytokeratins and lung carcinomas. Cesk Patol. 1999;35:80–84

80. Lyda MH, Weiss LM. Immunoreactivity for epithelial and neuroendocrine antibodies are useful in the differential diagnosis of lung carcinomas. Hum Pathol. 2000;31:980–987

81. Johansson L. Histopathologic classification of lung cancer: Relevance of cytokeratin and TTF-1 immunophenotyping. Ann Diagn Pathol. 2004;8:259–267

82. Pan CC, Chen PC, Tsay SH, et al. Differential immunoprofiles of hepatocellular carcinoma, renal cell carcinoma, and adrenocortical carcinoma: a systemic immunohistochemical survey using tissue array technique. Appl Immunohistochem Mol Morphol. 2005;13:347–352

83. Ordóñez NG. What are the current best immunohistochemical markers for the diagnosis of epithelioid mesothelioma? A review and update. Hum Pathol. 2007;38:1–16

84. Laury AR, Perets R, Piao H, et al. A comprehensive analysis of PAX8 expression in human epithelial tumors. Am J Surg Pathol. 2011;35:816–826

85. Puglisi F, Cesselli D, Damante G, et al. Expression of Pax-8, p53 and bcl-2 in human benign and malignant thyroid diseases. Anticancer Res. 2000;20:311–316

86. Zhang P, Zuo H, Nakamura Y, et al. Immunohistochemical analysis of thyroid-specific transcription factors in thyroid tumors. Pathol Int. 2006;56:240–245

87. Nonaka D, Tang Y, Chiriboga L, et al. Diagnostic utility of thyroid transcription factor Pax8 and TTF-2 (FOXE1) in thyroid epithelial neoplasms. Mod Pathol. 2008;21:192–200

88. Nonaka D, Chiriboga L, Soslow RA. Expression of pax8 as a useful marker in distinguishing ovarian carcinomas from mammary carcinomas. Am J Surg Pathol. 2008;32:1566–1571

89. Laury AR, Hornick JL, Perets R, et al. PAX8 reliably distinguishes ovarian serous tumors from malignant mesothelioma. Am J Surg Pathol. 2010;34:627–635

90. Long KB, Srivastava A, Hirsch MS, et al. PAX8 Expression in well-differentiated pancreatic endocrine tumors: correlation with clinicopathologic features and comparison with gastrointestinal and pulmonary carcinoid tumors. Am J Surg Pathol. 2010;34:723–729

91. Sangoi AR, Ohgami RS, Pai RK, et al. PAX8 expression reliably distinguishes pancreatic well-differentiated neuroendocrine tumors from ileal and pulmonary well-differentiated neuroendocrine tumors and pancreatic acinar cell carcinoma. Mod Pathol. 2011;24:412–424

Cited By:

This article has been cited 7 time(s).

Acta Cytologica
Thyroid Transcription Factor 1 and Napsin A Double Stain: Utilizing Different Vendor Antibodies for Diagnosing Lung Adenocarcinoma
Johnson, H; Cohen, C; Fatima, N; Duncan, D; Siddiqui, MT
Acta Cytologica, 56(6): 596-602.
Cancer Cytopathology
Endobronchial ultrasound fine-needle aspiration biopsy of pulmonary nonsmall cell carcinoma with subclassification by immunohistochemistry panel
Collins, BT
Cancer Cytopathology, 121(3): 146-154.
Modern Pathology
Value of PAX8, PAX2, napsin A, carbonic anhydrase IX, and claudin-4 immunostaining in distinguishing pleural epithelioid mesothelioma from metastatic renal cell carcinoma
Ordonez, NG
Modern Pathology, 26(8): 1132-1143.
Virchows Archiv
Tumor-to-tumor metastasis from lung cancer: a clinicopathological postmortem study
Matsukuma, S; Kono, T; Takeo, H; Hamakawa, Y; Sato, K
Virchows Archiv, 463(4): 525-534.
American Journal of Clinical Pathology
Napsin A Expression in Primary Mucin-Producing Adenocarcinomas of the Lung: An Immunohistochemical Study
Wu, J; Chu, PG; Jiang, Z; Lau, SK
American Journal of Clinical Pathology, 139(2): 160-166.
Modern Pathology
Mesothelioma with signet-ring cell features: report of 23 cases
Ordonez, NG
Modern Pathology, 26(3): 370-384.
Human Pathology
Application of immunohistochemistry in the diagnosis of epithelioid mesothelioma: a review and update
Ordonez, NG
Human Pathology, 44(1): 1-19.
Back to Top | Article Outline

napsin A; lung adenocarcinoma; renal cell carcinoma; immunohistochemistry

© 2012 Lippincott Williams & Wilkins, Inc.


Article Tools



Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.