Research ArticlesCombination of Napsin A and TTF-1 Immunohistochemistry Helps in Differentiating Primary Lung Adenocarcinoma From Metastatic Carcinoma in the LungYe, Jiqing MD, PhD; Findeis-Hosey, Jennifer J. MD; Yang, Qi AAS; McMahon, Loralee A. BA, HTL; Yao, Jorge L. MD; Li, Faqian MD, PhD; Xu, Haodong MD, PhDAuthor Information Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY This study was presented as a platform at the 99th Annual USCAP Meeting in Washington, DC, March 20-26, 2010. Reprints: Haodong Xu, MD, PhD, Department of Pathology and Laboratory Medicine, Box 626, University of Rochester Medical Center, Elmwood 601, Rochester, NY 14642 (e-mail: [email protected]). Received August 7, 2010 Accepted November 8, 2010 Applied Immunohistochemistry & Molecular Morphology: July 2011 - Volume 19 - Issue 4 - p 313-317 doi: 10.1097/PAI.0b013e318205b059 Buy Metrics Abstract Differentiation of primary from metastatic adenocarcinoma in the lung can be challenging, and it demands sensitive and specific biomarkers, especially when the tissue for diagnosis is limited. Thyroid transcription factor-1 (TTF-1) has been considered a reliable marker for adenocarcinoma of lung origin. However, several recent studies have shown that TTF-1 immunostaining is also positive in adenocarcinomas arising in different organs including colon, endometrium, endocervix, and ovary. In addition, approximately 20% of lung primary adenocarcinomas are negative for TTF-1 immunostaining, and napsin A immunostaining has slightly higher sensitivity in detecting lung primary adenocarcinoma. We performed TTF-1 and napsin A immunostaining on 120 cases of primary lung adenocarcinomas and 37 cases of metastatic carcinomas in the lung. The results showed that 95 (79.2%) of 120 lung primary adenocarcinomas showed napsin A(+)/TTF-1(+) double-positive immunostaining pattern. TTF-1(−)/napsin A(+), TTF-1(+)/napsin A(−), and TTF-1(−)/napsin A(−) were seen in 8.3%, 3.3%, and 9.2% lung primary adenocarcinomas, respectively. Eight (21.6%) of the 37 metastatic carcinomas were positive for TTF-1 and they include clear-cell renal cell carcinomas completely negative for napsin A although napsin A was detected in 12 (80.0%) of 15 primary papillary and 3 (33.3%) of 9 primary clear-cell renal cell carcinomas. All renal epithelial neoplasms were TTF-1 negative. These findings indicate that double napsin A and TTF-1-positive immunostaining is highly specific for lung primary adenocarcinoma and the combination of these 2 biomarkers is warranted to help segregating primary lung adenocarcinoma from metastatic carcinoma in the lung. © 2011 Lippincott Williams & Wilkins, Inc.