Napsin A, Aspartic proteinase napsin, TAO2

Napsin A is an asparatic protease with a molecular weight of approximately 38 kDa11, expressed in type-II pneumocytes and is involved in the N- and C-terminal processing of proSP-B in type-II pneumocytes9,10. TAO2 has been shown to be identical with Napsin A3. There is also a Napsin B gene which is transcribed exclusively in cells related to the immune system but lacks a stop codon and may represent a transcribed pseudogene2.

Immunohistochemical expression

It is expressed in the cytoplasm and is strongly positive in up to 80% of primary lung adenocarcinomas by immunohistochemistry. Poorly differentiated cancers do not stain as well as those that are well-differentiated. Squamous cell carcinomas and small cell carcinomas of the lung have been negative for napsin A. However, 10% of renal cell carcinomas and thyroid carcinomas are also positive. Renal and thyroid cancers may give false positive results, most likely because of the presence of intrinsic biotin, which can be detected on negative controls. Less than 5% of assorted adenocarcinomas, including those from the breast, pancreas, biliary tract, and colon stain with napsin A: expression, when present in breast and colonic adenocarcinomas, appears to be granular, unlike that in the lung7.

   

Napsin

Surfactant A

Surfactant B

TTF-1

 

Lung

adenocarcinoma

33/391, 47/583, 39/434, 70/835 , 17/21 5 , 10/126, 27/308, 79/8512, 122/15813

 

24/391, 44/835 , 17/21 5, 23/308, 71/1581

 

24/391

33/391, 8/126, 28/308, 69/9512,

127/15813

Pulmonary adenocarcinoma with enteric differentiation

0/78

1/78

 

3/78

large cell carcinoma

2/111, 2/73, 2/74, 3/912

3/111

1/111

6/111, 4/912

squamous cell carcinoma

0/311, 0/265, 0/4612, 0/391 , 9/35

4/311, 0/265, 0/3913

5/311

4/311, 0/4812, 0/3913

small cell carcinoma

0/151, 0/65, 0/312

0/151, 0/65

1/151

12/151, 1/312

non small cell carcinoma, not otherwise specified

5/1212

 

 

3/1212

carcinoid

0/61, 0/312

0/61

0/61

3/61, 2/312

other tumours

mesothelioma

0/54, 0/56, 0/3812

 

 

0/56, 0/3812

melanoma

0/41

0/41

0/41

0/41

breast

0/255, 0/86, 0/1712

0/255

 

0/86, 0/1712

renal cell carcinoma

1/11, 49/11812

0/11

0/11

0/11, 0/11812

gastric carcinoma

0/11, 0/26

0/11

0/11

0/11, 0/6

colonic carcinoma

0/11, 0/385, 0/16, 0/148, 0/512

0/11, 0/385, 0/148

0/11

0/11, 0/16, 0/148, 0/512

pancreas

0/16, 0/3112

 

 

0/16, 0/3112

salivary gland carcinoma

0/11 , 0/1 5

1/11 , 0/1 5

1/11

0/11

prostatic carcinoma

0/11

0/11

0/11

0/11

urothelial carcinoma of bladder

0/26

 

 

0/26

ovary

0/76

 

 

0/76

endometrium

0/5 , 0/16

0/5

 

0/16

thyroid

0/21 5, 2/8112

0/21 5

 

80/8112

germ cell embryonic carcinoma

0/11

0/11

1/11

0/11

basal cell carcinoma

0/11

0/11

0/11

0/11

sarcoma

0/51

0/51

0/51

0/51

various adenocarcinomas

0/334

 

 

 

           

Diagnostic utility

References

1 Ueno T, Linder S,Elmberger G. Aspartic proteinase napsin is a useful marker for diagnosis of primary lung adenocarcinoma. Br J Cancer 2003; 88:1229-33 FULL TEXT

2 Tatnell PJ, Powell DJ, Hill J, et al. Napsins: new human aspartic proteinases. Distinction between two closely related genes. FEBS Lett 1998; 441:43-8

3 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; 91:1015-21

4 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; 41:155-62

5 Suzuki A, Shijubo N, Yamada G, et al. Napsin A is useful to distinguish primary lung adenocarcinoma from adenocarcinomas of other organs. Pathol Res Pract 2005; 201:579-86

6 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; 35:493-7

7 Jagirdar J Application of immunohistochemistry to the diagnosis of primary and metastatic carcinoma to the lung. Arch Pathol Lab Med 2008; 132:384-96 FULL TEXT

8 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; 29:660-5

9 Ueno T, Linder S, Na CL, et al. Processing of pulmonary surfactant protein B by napsin and cathepsin H. J Biol Chem 2004; 279:16178-84

10 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; 278:49006-14

11 Schauer-Vukasinovic V, Bur D, Kling D, et al. Human napsin A: expression, immunochemical detection, and tissue localization. FEBS Lett 1999; 462:135-9

12 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 Jan;41(1):20-5. (TTF-1 clone 8G7G3/1 used, confirmed by author)

13 Yang M, Nonaka D. A study of immunohistochemical differential expression in pulmonary and mammary carcinomas. Mod Pathol. 2010 May;23(5):654-61. (with corrections to the paper provided by author)

14  Pereira TC, Share SM, Magalhaes AV, Silverman JF. 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 Jan;19(1):10-4.

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; 462:129-34

 

This page last revised 16.4.2011.

©SMUHT/PW Bishop