title: 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.
abstract: BACKGROUND
  Differentiation of non-small cell carcinoma into histologic types is important because of new, successful therapies that target lung adenocarcinoma (ACA). TTF-1 is a favored marker for lung ACA but has limited sensitivity and specificity. Napsin A (Nap-A) is a functional aspartic proteinase that may be an alternative marker for primary lung ACA.
  
  
  OBJECTIVE
  To compare Nap-A versus TTF-1 in the typing of primary lung carcinoma and the differentiation of primary lung ACA from carcinomas of other sites.
  
  
  METHODS
  Immunohistochemistry for Nap-A and TTF-1 was performed on tissue microarrays of 1674 cases of carcinoma: 303 primary lung ACAs (18.1%), 200 primary squamous cell lung carcinomas (11.9%), 52 primary small cell carcinomas of the lung (3.1%), and carcinomas of the kidney (n  =  320; 19.1%), thyroid (n  =  96; 5.7%), biliary (n  =  89; 5.3%), bladder (n  =  47; 2.8%), breast (n  =  93; 5.6%), colon (n  =  95; 5.7%), liver (n  =  96; 5.7%), ovaries (n  =  45; 2.7%), pancreas (n  =  48; 2.9%), prostate (n  =  49; 2.9%), stomach (n  =  93; 5.6%), and uterus (n  =  48; 2.9%). Cases were evaluated against a negative control as negative, weak positive, and strong positive.
  
  
  RESULTS
  Nap-A was more sensitive than TTF-1 for primary lung ACA (87% versus 64%; P < .001). Nap-A was more specific than TTF-1 for primary lung ACA versus all tumors, excluding kidney, independent of tumor type (P < .001).
  
  
  CONCLUSIONS
  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(+)).
authors.affiliation: Department of Pathology, University of Texas Health Science Center, San Antonio, USA.
authors.forename: Bradley M
authors.initials: BM
authors.lastname: Turner
authors.forename: Philip T
authors.initials: PT
authors.lastname: Cagle
authors.forename: Irma M
authors.initials: IM
authors.lastname: Sainz
authors.forename: Junya
authors.initials: J
authors.lastname: Fukuoka
authors.forename: Steven S
authors.initials: SS
authors.lastname: Shen
authors.forename: Jaishree
authors.initials: J
authors.lastname: Jagirdar
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism; D000328:Adult; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000175:diagnosis* / Q000378:metabolism; D003937:Diagnosis, Differential; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D012680:Sensitivity and Specificity; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D016282:Aspartic Acid Endopeptidases; C498549:NAPSA protein, human