Napsin A

Synonyms: NAPSA, TA02

by Jan Klos

Background

Napsin A is an enzyme (aspartic proteinase) with a molecular weight of approximately 38 kDa encoded by NAPSA gene localized to chr 19q13.33. The protein is homologous with the polypeptide TA02 (detected by gel electrophoresis of lung adenocarcinomas). It is probably involved in the maturation of surfactant protein B in lungs while its function in kidney epithelium is less known.

Staining pattern: cytoplasmic granular.

Expression in normal tissues:  type II pneumocytes as well as in epithelium of the proximal and convoluted tubules of the kidney. In lungs it is localized to lamellar bodies together with surfactant protein B.  Positive staining is also seen in alveolar macrophages presumably secondary to phagocytosis.

Expression in tumors

  • Primary lung adenocarcinomas are positive in >80% in areas with glandular differentiation.
  • Lung adenocarcinomas with enteric differentiation are positive in 40-50%.
  • Squamous cell carcinomas and small cell carcinomas of the lung are negative.
  • Clear cell carcinoma of the ovary is positive in >90% and clear cell carcinomas of uterus is stained in ~60% of cases
  • Renal cell carcinomas show variation depending on type from 10% positive chromophobe carcinomas and ~40% positive clear cell carcinomas to 80% positive renal papillary carcinomas
  • Thyroid carcinomas are positive in less than 10%.
  • Other adenocarcinomas including those from the breast, liver, ovary, uterus, pancreas, biliary tract and colon are reported positive in less than 5%.

Monoclonal antibodies are recommended since polyclonal antibodies may give nonspecific staining  in supranuclear part of the cells (reminding of MAG) in mucinous carcinomas from other sites than lungs.

Control tissue

Kidney or lung.

Application

  • Subtyping of lung carcinoma. Positive reaction with Napsin A and/or TTF-1 favours adenocarcinoma of the lung, while positive reaction with CK5/6 and/or P40/P63 favours squamous cell carcinoma.
  • Subtyping of ovarian/endometrial adenocarcinoma – recommended to use in panel including at least PAX8 and WT-1.
  • Positive staining is seen in 50% renal cell carcinomas.
  • Identification of origin of metastatic adenocarcinomas (in panel with other antibodies).

Selected references

  1. 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. Epub 2009 Sep 8.
  2. 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 Aug;35(8):493-7.
  3. Fadare O1, Desouki MM, Gwin K, et al. Frequent expression of napsin A in clear cell carcinoma of the endometrium: potential diagnostic utility. Am J Surg Pathol. 2014 Feb;38(2):189-96. doi: 10.1097/PAS.0000000000000085.
  4. 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 May;29(5):660-5.
  5. Iwamoto M1, Nakatani Y2, Fugo K3, et al. Napsin A is frequently expressed in clear cell carcinoma of the ovary and endometrium. Hum Pathol. 2015 Jul;46(7):957-62. doi: 10.1016/j.humpath.2015.03.008. Epub 2015 Apr 11.
  6. Jagirdar J. Application of immunohistochemistry to the diagnosis of primary and metastatic carcinoma to the lung. Arch Pathol Lab Med 2008 Mar;132(3):384-96.
  7. Ordonez NG. Napsin A expression in lung and kidney neoplasia: a review and update. Adv Anat Pathol. 2012 Jan;19(1):66-73.
  8. Turner BM, Cagle PT, Sainz IM, et al. Napsin A, a new marker for lung adenocarcinoma, is complementary and more sensitive and specific than thyroid transcription factor 1 in the differential diagnosis of primary pulmonary carcinoma: evaluation of 1674 cases by tissue microarray.  Arch Pathol Lab Med. 2012 Feb;136(2):163-71.
  9. Whithaus K, Fukuoka J, Prihoda TJ, et al. Evaluation of napsin A, cytokeratin 5/6, p63, and thyroid transcription factor 1 in adenocarcinoma versus squamous cell carcinoma of the lung. Arch Pathol Lab Med. 2012 Feb;136(2):155-62. 
  10. Yatabe Y, Dacic S, Borczuk AC et al. Best Practices Recommendations for Diagnostic Immunohistochemistry in Lung Cancer. J Thorac Oncol. 2019 Mar;14(3):377-407. doi: 10.1016/j.jtho.2018.12.005. Epub 2018 Dec 18.PMID: 30572031.