Which pattern would most strongly argue against a breast origin?

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

Answer: (C)

Immunohistochemical profiling helps determine where a metastatic carcinoma likely originated by looking at marker patterns. GATA3 is commonly expressed in breast cancers, so a pattern with GATA3 positivity and Napsin A negativity would support a breast origin. In contrast, Napsin A and TTF-1 are markers that favor lung adenocarcinoma; TTF-1 is especially specific for lung tumors, and Napsin A is frequently positive in them. When both Napsin A and TTF-1 are positive, the profile points strongly to a pulmonary primary and argues against breast origin, since breast carcinomas are rarely TTF-1 positive and often lack Napsin A expression. So the combination of Napsin A positive and TTF-1 positive is the strongest indicator against a breast origin.