The use of PAX8, PSA, GATA-3 and estrogen receptors may be helpful in the differential diagnosis, because lung adenocarcinomas essentially show negative nuclear staining for these markers, excluding the possibility of metastatic disease from a carcinoma of Müllerian (PAX8), prostatic (PSA), urothelial (GATA-3), or mammary (GATA-3 and estrogen receptors) origin. The gene discussed is ESR1; the disease is metastatic neoplasm.