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.
Napsin A is detected in most cases of non-mucinous lung AC (60-90%, lowest in low differentiated subtypes) and papillary RCC (70%).
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.
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.
Agackiran Y, Ozcan A, Akyurek N, Memis L, Findik G, Kaya S. Desmoglein-3 and Napsin A double stain, a useful immunohistochemical marker for differentiation of lung squamous cell carcinoma and adenocarcinoma from other subtypes. Appl Immunohistochem Mol Morphol. 2012 Jul;20(4):350-5. doi: 10.1097/PAI.0b013e318245c730. PubMed PMID: 22495379. Chernock RD, El-Mofty SK, Becker N, Lewis JS Jr. Napsin A Expression in Anaplastic, Poorly Differentiated, and Micropapillary Pattern Thyroid Carcinomas. Am J Surg Pathol. 2013 May 15. [Epub ahead of print] PubMed PMID: 23681073. Iqbal J. Role of Napsin A and TTF1 as a diagnostic marker for lung adenocarcinoma. Arch Pathol Lab Med. 2013 Feb;137(2):155. doi: 10.5858/arpa.2012-0123-LE. PubMed PMID: 23368855. Johnson H, Cohen C, Fatima N, Duncan D, Siddiqui MT. Thyroid transcription factor 1 and Napsin A double stain: utilizing different vendor antibodies for diagnosing lung adenocarcinoma. Acta Cytol. 2012;56(6):596-602. doi: 10.1159/000339793. Epub 2012 Nov 24. PubMed PMID: 23207437. Kim MJ, Shin HC, Shin KC, Ro JY. Best immunohistochemical panel in distinguishing adenocarcinoma from squamous cell carcinoma of lung: tissue microarray assay in resected lung cancer specimens. Ann Diagn Pathol. 2013 Feb;17(1):85-90. doi: 10.1016/j.anndiagpath.2012.07.006. Epub 2012 Oct 4. PubMed PMID: 23040737. Mukhopadhyay S, Katzenstein AL. Comparison of monoclonal napsin A, polyclonal napsin A, and TTF-1 for determining lung origin in metastatic adenocarcinomas. Am J Clin Pathol. 2012 Nov;138(5):703-11. doi: 10.1309/AJCPKVBXTI9O3TEM. PubMed PMID: 23086771. Mukhopadhyay S, Katzenstein AL. 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. Am J Surg Pathol. 2011 Jan;35(1):15-25. doi: 10.1097/PAS.0b013e3182036d05. PubMed PMID: 21164283. Ordóñez NG. A word of caution regarding napsin A expression in squamous cell carcinomas of the lung. Am J Surg Pathol. 2012 Mar;36(3):396-401. doi: 10.1097/PAS.0b013e31823b13e2. PubMed PMID: 22198009. Ordóñez NG. Napsin A expression in lung and kidney neoplasia: a review and update. Adv Anat Pathol. 2012 Jan;19(1):66-73. doi: 10.1097/PAP.0b013e31823e472e. Review. PubMed PMID: 22156835. Ordóñez NG. Value of PAX8, PAX2, napsin A, carbonic anhydrase IX, and claudin-4 immunostaining in distinguishing pleural epithelioid mesothelioma from metastatic renal cell carcinoma. Mod Pathol. 2013 Mar 15. doi: 10.1038/modpathol.2013.34. [Epub ahead of print] PubMed PMID: 23503645. Turner BM, Cagle PT, Sainz IM, Fukuoka J, Shen SS, Jagirdar J. 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. doi: 10.5858/arpa.2011-0320-OA. PubMed PMID: 22288963. Whithaus K, Fukuoka J, Prihoda TJ, Jagirdar J. 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. doi: 10.5858/arpa.2011-0232-OA. PubMed PMID: 22288962. Wu J, Chu PG, Jiang Z, Lau SK. Napsin A expression in primary mucin-producing adenocarcinomas of the lung: an immunohistochemical study. Am J Clin Pathol. 2013 Feb;139(2):160-6. doi: 10.1309/AJCP62WJUAMSZCOM. PubMed PMID: 23355200. Xu B, Abourbih S, Sircar K, Kassouf W, Aprikian A, Tanguay S, Brimo F. Diagnostic and Prognostic Role of Immunohistochemical Expression of Napsin-AAspartic Peptidase in Clear Cell and Papillary Renal Cell Carcinoma: A Study Including 233 Primary and Metastatic Cases. Appl Immunohistochem Mol Morphol. 2013 May 22. [Epub ahead of print] PubMed PMID: 23702650. Ye J, Findeis-Hosey JJ, Yang Q, McMahon LA, Yao JL, Li F, Xu H. Combination of napsin A and TTF-1 immunohistochemistry helps in differentiating primary lung adenocarcinoma from metastatic carcinoma in the lung. Appl Immunohistochem Mol Morphol. 2011 Jul;19(4):313-7. doi: 10.1097/PAI.0b013e318205b059. PubMed PMID: 21464700. Ye J, Hameed O, Findeis-Hosey JJ, Fan L, Li F, McMahon LA, Yang Q, Wang HL, Xu H. Diagnostic utility of PAX8, TTF-1 and napsin A for discriminating metastatic carcinoma from primary adenocarcinoma of the lung. Biotech Histochem. 2012 Jan;87(1):30-4. doi: 10.3109/10520295.2011.591838. Epub 2011 Aug 15. PubMed PMID: 21838611. Zhang P, Han YP, Huang L, Li Q, Ma DL. Value of napsin A and thyroid transcription factor-1 in the identification of primary lung adenocarcinoma. Oncol Lett. 2010 Sep;1(5):899-903. Epub 2010 Sep 1. PubMed PMID: 22966403; PubMed Central PMCID: PMC3436431.