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19q13.33 HGNC:13395 MIM.605631

Friday 14 January 2011


- 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.


- 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