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In Search of the Ideal Immunopanel to Distinguish Metastatic Mammary Carcinoma From Primary Lung Carcinoma: A Tissue Microarray Study of 207 Cases

Kawaguchi, Kathy R. MD*; Lu, Fang-I. MD; Kaplan, Rachel MD*; Liu, Yi-Fang MD*; Chadwick, Paul BA*; Chen, Zhengming PhD; Brogi, Edi MD; Shin, Sandra J. MD*

Applied Immunohistochemistry & Molecular Morphology: April 2014 - Volume 22 - Issue 4 - p 266–274
doi: 10.1097/PAI.0b013e318297cc0b
Research Articles

Background: Distinguishing metastatic carcinoma of breast origin (MCBO) to lung from primary lung carcinomas (PLC) is a diagnostic quandary with clinical ramifications. Immunostains CK7, CK20, ER, PR, and Mammaglobin as well as pertinent negative stains are utilized but prove insufficient. We set out to identify stains either alone or as a group that would better discern between these 2 entities.

Design: Tissue microarrays of 109 MCBO to lung and 102 PLC were stained with CK7, CK20, ER, PR, AR, Mammaglobin, Napsin A, GATA-3, and TTF-1. An H-score was calculated for each case and stain.

Results: The highest area under the receiver-operating characteristic curves for each stain was seen with GATA-3 (0.817), Napsin A (0.817), and TTF-1 (0.854). When all possible combinations were analyzed, GATA-3 and TTF-1 proved to correctly classify with the highest accuracy (0.934). Combinations of GATA-3 and Napsin A (0.920) and GATA-3, Napsin A, and TTF-1 (0.933) were not significantly different from GATA-3 and TTF-1. The odds ratios for each stain and combination of stains showed that those for GATA-3 and TTF-1 were divergent, signifying that cases with higher H-scores for GATA-3 and TTF-1 were more likely to be classified as MCBO and PLC, respectively.

Conclusions: GATA-3 and TTF-1 can correctly classify a case as either MCBO or PLC in 93.4% of cases. Although highly specific and sensitive for PLC, Napsin A in lieu of TTF-1 or as an additional stain did not improve classification accuracy.

Departments of *Pathology and Laboratory Medicine

Public Health, Division of Biostatistics and Epidemiology, Weill Cornell Medical College

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY

K.R.K. and F.-I.L. contributed equally as cofirst authors.

Presented at the United States and Canadian Academy of Pathology 100th Annual Meeting, 2011, San Antonio, TX.

The authors declare no conflict of interest.

Reprints: Kathy R. Kawaguchi, MD, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Starr 1036, 525 E. 68th Street, New York, NY 10065 (e-mail:

Received November 30, 2012

Accepted April 18, 2013

© 2014 Lippincott Williams & Wilkins, Inc.