Which pattern would suggest lung origin rather than breast origin?

• A. Napsin A +, TTF-1 +
• B. GATA3 +, Napsin A-
• C. Napsin A +, GATA3 -
• D. GATA 3+, ER/PR/HER2(-/+)

Answer: (A)

Immunohistochemical profiling is used to infer where a carcinoma originated. Certain markers are characteristic of specific tissues. Napsin A and TTF-1 are strongly associated with lung tissue, especially lung adenocarcinoma. Napsin A is commonly expressed in type II pneumocytes and many lung cancers, while TTF-1 is a nuclear factor routinely positive in lung tumors. When a tumor is positive for both Napsin A and TTF-1, it most strongly points to a pulmonary origin.

GATA3, on the other hand, is a marker that favors breast (and some urothelial) tumors, and ER/PR/HER2 status is typically used to profile breast cancers. So a pattern with GATA3 positivity would lean toward breast origin, whereas the combination of Napsin A and TTF-1 positivity most clearly supports a lung origin.