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

type II pneumocytes (within lysosomes) and alveolar macrophages (probably secondary to phagocytosis)
kidney

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

Lung

33/391, 47/583, 39/43(granular cytoplasmic staining)4, 70/835 , 17/21(nodal metastases) 5 , 10/126, 27/308, 79/8512, 122/15813

24/391, 44/835 , 17/21(nodal metastases) 5, 23/308, 71/1581

24/391

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

Pulmonary adenocarcinoma with enteric differentiation

0/78

1/7(1 case 5-50% positive)8

large cell carcinoma

2/111, 2/73, 2/74, 3/9(using TMAs and clone 8G7G3/1) 12

3/111

1/111

6/111, 4/9(using TMAs and clone 8G7G3/1) 12

squamous cell carcinoma

0/311, 0/265, 0/46(using TMAs and clone 8G7G3/1) 12, 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, 0/3(using TMAs and clone 8G7G3/1) 12

0/151, 0/65

1/151

12/151, 1/3(using TMAs and clone 8G7G3/1) 12

non small cell carcinoma, not otherwise specified

5/12(using TMAs and clone 8G7G3/1) 12

3/12(using TMAs and clone 8G7G3/1) 12

0/61, 0/3(using TMAs and clone 8G7G3/1) 12

0/61

0/61

3/61, 2/3(using TMAs and clone 8G7G3/1) 12

other tumours

0/54, 0/56, 0/38(using TMAs and clone 8G7G3/1) 12

0/56, 0/38(using TMAs and clone 8G7G3/1) 12

0/4(metastases to lung)1

0/4(metastases to lung)1

0/4(metastases to lung)1

0/4(metastases to lung)1

breast

0/255, 0/86, 0/17(using TMAs and clone 8G7G3/1) 12

0/86, 0/17(using TMAs and clone 8G7G3/1) 12

renal cell carcinoma

1/1(metastasis to lung)1, 49/11812

0/1(metastasis to lung)1

0/1(metastasis to lung)1

0/1(metastasis to lung)1, 0/11812

gastric carcinoma

0/1(metastasis to lung)1, 0/26

0/1(metastasis to lung)1

0/1(metastasis to lung)1

0/1(metastasis to lung)1, 0/6

colonic carcinoma

0/1(metastasis to lung)1, 0/385, 0/16, 0/148, 0/5(using TMAs and clone 8G7G3/1) 12

0/1(metastasis to lung)1, 0/385, 0/148

0/1(metastasis to lung)1

0/1(metastasis to lung)1, 0/16, 0/148, 0/5(using TMAs and clone 8G7G3/1) 12

pancreas

0/16, 0/31(using TMAs and clone 8G7G3/1) 12

0/16, 0/31(using TMAs and clone 8G7G3/1) 12

salivary gland carcinoma

0/1(metastasis to lung)1 , 0/1(lung metastases) 5

1/1(metastasis to lung)1 , 0/1(lung metastases) 5

1/1(metastasis to lung)1

0/1(metastasis to lung)1

prostatic carcinoma

0/1(metastasis to lung)1

0/1(metastasis to lung)1

0/1(metastasis to lung)1

0/1(metastasis to lung)1

urothelial carcinoma of bladder

ovary

endometrium

thyroid

0/21 5, 2/81(using TMAs and clone 8G7G3/1) 12

germ cell embryonic carcinoma

0/1(metastasis to lung)1

0/1(metastasis to lung)1

1/1(metastasis to lung)1

0/1(metastasis to lung)1

basal cell carcinoma

0/1(metastasis to lung)1

0/1(metastasis to lung)1

0/1(metastasis to lung)1

0/1(metastasis to lung)1

sarcoma

0/5(metastases to lung)1

0/5(metastases to lung)1

0/5(metastases to lung)1

0/5(metastases to lung)1

various adenocarcinomas

0/334

Diagnostic utility

Identifying an adenocarcinoma as primary of the lung.

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