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

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. 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. 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. 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). 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(+)).