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19q13.33 HGNC:13395 MIM.605631

Friday 14 January 2011

napsin A aspartic peptidase; Napsin-A

Definition: Napsin A is an aspartic proteinase of the pepsin family involved in the maturation of surfactant protein B. It is expressed primarily in lung and kidney.


- Napsin-A, a new marker for lung adenocarcinoma

Expression in normal cells

- Type 2 pneumocytes (cytoplasm)
- alveolar macrophages (cytoplasm) (Hum Pathol 2010;41:20)

Expression in tumoral cells

- Pulmonary adenocarcinoma

- Renal cell carcinoma: papillary (80%), clear cell (33%, Appl Immunohistochem Mol Morphol 2011;19:313)

- ovarian clear cell carcinoma (Mod Pathol 2015;28;111) and ovarian endometrioid carcinoma

- Thyroid carcinoma:

  • anaplastic (15%, Am J Surg Pathol 2013;37:1215),
  • micropapillary (2 of 2),
  • papillary (5% [2 cases, both were tall cell], Hum Pathol 2010;41:20),
  • poorly differentiated (13%)


- pulmonary adenocarcinoma

  • Nap-A is superior to TTF-1 in distinguishing primary lung ACA from other carcinomas (except kidney), particularly primary lung small cell carcinoma, and primary thyroid carcinoma.
  • A combination of Nap-A and TTF-1 is useful in the distinction of primary lung ACA (Nap-A+, TTF-1+) from primary lung squamous cell carcinoma (Nap-A−, TTF-1−) and primary lung small cell carcinoma (Nap-A−, TTF-1+).
  • Useful individually or as part of panel to distinguish lung adenocarcinoma (positive) from squamous cell carcinoma (negative in tumor cells, but positive in hyperplastic type II pneumocytes and intra-alveolar macrophages entrapped within tumor cells)
  • Useful as part of panel to classify poorly differentiated non small cell lung carcinoma on small biopsies or fine needle aspirates (Cytojournal 2012;9:10) or bronchial brushings (Cancer Cytopathol 2011;119:335)
  • Superior to TTF1 in distinguishing primary lung adenocarcinoma from other carcinomas (except kidney), particularly primary lung small cell carcinoma and primary thyroid carcinoma (Arch Pathol Lab Med 2012;136:163)
  • Superior to TTF1 in distinguishing metastatic pulmonary (positive) from non-pulmonary (negative) adenocarcinoma in cell blocks prepared from malignant pleural effusions (Acta Cytol 2011;55:266) or from fine needle aspirates (Cancer Cytopathol 2011;119:127)
  • May help identify metastatic disease with unknown primary as originating in lung (Case Rep Oncol 2011;4:564)
  • May help distinguish lung primaries from metastases to lung, as part of panel (Biotech Histochem 2012;87:30)
  • Lack of NapsinA expression in tumor cells may be poor prognostic marker in pulmonary adenocarcinoma (Lung Cancer 2012;77:156)


- YRC:239 : Brain - Metastatic poorly differentiated pulmonary adenocarcinoma - Napsin A immunostain.

Definition: The activation peptides of aspartic proteinases plays role as inhibitors of the active site. These peptide segments, or pro-parts, are deemed important for correct folding, targeting, and control of the activation of aspartic proteinase zymogens.

The pronapsin A gene is expressed predominantly in lung and kidney. Its translation product is predicted to be a fully functional, glycosylated aspartic proteinase precursor containing an RGD motif and an additional 18 residues at its C-terminus.

Napsin A is a novel peripheral airway epithelial marker that, because it is commonly expressed in lung adenocarcinomas but absent in squamous cell carcinomas, is considered to be useful in distinguishing between these 2 types of tumors.

Recent immunohistochemical studies, however, have reported napsin A expression in up to 26% of squamous cell carcinomas of the lung, a finding that indicates that this marker may not be as specific for lung adenocarcinomas as is generally believed.

In a series, none of the 90 squamous cell carcinomas of the lung exhibited napsin A positivity in the neoplastic cells; however, because strong napsin A reactivity was observed in hyperplastic type II pneumocytes and in intra-alveolar macrophages, both of which were sometimes seen entrapped within the tumor, it has been concluded that the presence of these entrapped cells was the most likely cause of the discrepancies. (22198009)

Pathologists should be aware of this potential pitfall in the interpretation of the immunostaining for napsin A, especially when small lung biopsy specimens, tissue microarrays, or cytology specimens are being evaluated.

See also

- NAPSs : napsins

Paywall References

- 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. 2012. doi : 10.5858/arpa.2011-0320-OA

- A word of caution regarding napsin a expression in squamous cell carcinomas of the lung. Ordóñez NG. Am J Surg Pathol. 2012 Mar;36(3):396-401. PMID: 22198009

- 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. Mukhopadhyay S, Katzenstein AL. Am J Surg Pathol. 2011 Jan;35(1):15-25. PMID: 21164283