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

<jats:p>Context.—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.</jats:p><jats:p>Objectives.—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.</jats:p><jats:p>Design.—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.</jats:p><jats:p>Results.—Nap-A was more sensitive than TTF-1 for primary lung ACA (87% versus 64%; P &lt; .001). Nap-A was more specific than TTF-1 for primary lung ACA versus all tumors, excluding kidney, independent of tumor type (P &lt; .001).</jats:p><jats:p>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+).</jats:p>