Which option would you use to confirm breast origin if ER/PR/HER2 are negative?

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

Answer: (D)

The main idea is using lineage-specific markers to determine where a tumor comes from when hormone receptor status isn’t informative. GATA3 is a marker strongly associated with breast epithelium and is expressed in most breast carcinomas, including many triple-negative cases. So, if ER, PR, and HER2 are negative, finding GATA3 positivity provides solid evidence that the tumor is of breast origin, rather than from another site.

Napsin A and TTF-1 point toward lung origin; if those were positive, it would argue against breast origin. Therefore, a profile showing GATA3 positivity with negative or non-definitive hormone receptors best supports a breast primary in this scenario.