Napsin A
Synonyms: Aspartyl protease 4 (ASP4), EC3.4.23, Kdap, napsin 1, SNAPA, TA01/TA02.
Nature: Cytoplasmic aspartic protease belonging to the peptidase A1 family, 420 amino acids, 45 kDa, encoded by the NSPSA gene located on Chr 19q13.3.
Function and occurrence: Napsin A is predominantly expressed in the lung and kidney. In the lung, Napsin A is expressed in alveolar type II pneumocytes, regulated by TTF-1, and is involved in the generation of the surfactant protein B. Intra-alveolar macrophages contain Napsin A as a result of phagocytosis. In the kidney, Napsin A is expressed in the proximal tubules, where it is involved in lysosomal protein catabolism.
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Napsin A is detected in most cases of non-mucinous lung AC (60-90%, lowest in low differentiated subtypes) and papillary RCC (70%).
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Napsin A is detected less frequently in lung mucinous adenocarcinoma and large cell carcinoma (20-30%) and clear cell renal cell carcinoma (10-40% - often focal reaction).
-(+)
In most studies Napsin A is not detected in lung squamous cell carcinoma. Focal staining have been described in up to 20% but this has been questioned. Napsin A positivity in up to 5% of thyroid carcinoma (papillary and low differentiated) have been reported.
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Napsin A has not been detected in lung carcinoid and small cell carcinoma. Napsin A has only rarely been found in chromophobic renal cell carcinoma and not in renal oncocytoma. Carcinomas of e.g., breast, stomach, colorectum, pancreas, liver, ovary, and endometrium has not been found Napsin A positive.
Napsin A is important in the differential diagnosis of lung adenocarcinoma vs. squamous cell carcinoma, used in a panel with TTF-1, CK5 and p63, and vs. mesothelioma in pleura related neoplasms, used in a panel with e.g., TTF-1, Calretinin and Podoplanin. Napsin A has approximately the same sensitivity as TTF1 but the specificity is higher. For tumours presenting as adenocarcinoma of unknown origin, the identification of a lung origin may be aided by Napsin A together with TTF1, and renal origin by Napsin A together with PAX8. Napsin A has less relevance in subclassification of primary renal tumours.
Both kidney and lung can be used as positive tissue control for Napsin A. However, in concordance with the previous assessments for Napsin A in NordiQC (run 39, 2013), kidney was found more informative for an appropriate calibration of the protocol. In kidney virtually all epithelial cells of the proximal tubules must show an at least moderate, distinct granular cytoplasmic staining reaction. Type II pneumocytes and alveolar macrophages of the lung showed a high staining intensity independent of protocol parameters applied and lung tissue is thus less useful to calibrate the protocol for the demonstration of Napsin A in low-level antigen expressing cells and neoplasias. Colon is useful as negative control; no staining should be seen in the columnar epithelial cells and macrophages.
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