Which option represents a breast-origin signature with variable receptor status?

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

Answer: (A)

The key idea is using lineage-specific markers to identify the tumor’s origin while recognizing that receptor status can vary in breast cancers. GATA3 is a marker strongly associated with breast tissue, so a tumor that is GATA3 positive supports a breast origin. At the same time, the receptors ER, PR, and HER2 can be either positive or negative across different breast cancers (and even within a single tumor’s metastases), so a signature described as ER/PR/HER2 with variable (negative or positive) status fits breast origin with fluctuating receptor profiles.

In contrast, markers like Napsin A and TTF-1 are more characteristic of lung adenocarcinoma; a profile with Napsin A positivity or TTF-1 positivity would point toward lung rather than breast origin. Thus, GATA3 positivity with variable ER/PR/HER2 status best represents a breast-origin signature with variable receptor status.