Aberrant expression of GATA3 in metastatic adenocarcinoma of the prostate: an important pitfall

• Published in: Histopathology 2024-02, Vol.84 (3), p.507-514
• Main Authors: Lobo, João, Tenace, Nazario P, Cañete‐Portillo, Sofia, Carneiro, Isa, Henrique, Rui, Lucianò, Roberta, Harik, Lara R, Magi‐Galluzzi, Cristina
• Format: Article
• Language: English
• Subjects: aberrant expression; Adenocarcinoma; GATA-3 protein; GATA3; Immunohistochemistry; Metastases; Metastasis; metastatic; NKX3.1; Nkx3.1 protein; Pathology; Prostate cancer; prostatic adenocarcinoma; Urothelial carcinoma
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/his.15094

Aims The distinction of high‐grade prostate cancer (PCa) from poorly differentiated urothelial carcinoma (UC) can be somewhat challenging on clinical and morphological grounds alone, yet it is of great importance for prognostication and choice of treatment. GATA3 is a useful immunohistochemical marker to confirm urothelial origin. However, recent works report strong GATA3 immunoexpression in primary high‐grade PCa. The aim of this study was to explore GATA3 expression specifically in metastatic PCa. Methods and results The pathology databases of four tertiary institutions were queried for cases of metastatic PCa. Available slides and clinical records were reviewed by experienced genitourinary pathologists. Prostatic markers (PSA, PSAP, NKX3.1) and GATA3 immunohistochemistry were performed. A total of 163 metastatic PCa cases were included. At least one prostate marker was positive in each case of non‐regional distant metastasis, confirming prostatic origin. GATA3 strong staining was found in four (2.5%) cases: two liver, one bone and one non‐regional lymph‐node metastases. All four patients had Grade Group 5 PCa at the initial diagnosis. The metastatic prostatic adenocarcinomas were solid, either with no gland formation (n = 3) or with only focal cribriforming (n = 1). Conclusions To our knowledge, this is the first study exploring GATA3 expression specifically in metastatic PCa. Despite being infrequent, GATA3 positivity in high‐grade PCa may lead to misdiagnosis, with clinical implications. We recommend a panel of immunohistochemical markers, both prostatic and urothelial, for ruling out UC, either in primary tumour samples or in the event of metastases of unknown primary, when a genitourinary origin is suspected. Accurate discrimination of metastatic prostate cancer from urothelial cancer is important for prognostication and therapy. GATA3 positivity occurred in 2.5% of metastatic prostate cancer cases (all being predominantly solid), constituting an important pitfall. Combined panels of immunohistochemistry (prostatic and urothelial markers) are recommended for accurate diagnosis.