Utility of TRPS1 Compared to GATA3, and SOX10 Immunohistochemistry in Diagnosis and Prognosis of Breast cancer Molecular Subtypes

Whenever metastatic carcinoma is suspected in female patients, with tumors in organs such as lung, liver, bone, or brain, metastatic breast cancer is always included in the differential diagnosis, even in the absence of a documented clinical history. This is because breast cancer is the most common cancer in females, and 20–30 % of progress to metastatic disease [1]. To determine the primary site of carcinoma, a sensitive and specific tumor marker is necessary in addition to the patient's tumor histology and clinical history.

The most aggressive and undifferentiated phenotype of breast cancer is TNBC [2], which also has a high relapse rate and early metastasis. Metastatic poorly differentiated TNBC often lacks substantial tumor markers for its breast origin. Mammaglobin, gross cystic disease fluid protein 15 (GCDFP15), and GATA-binding protein 3 (GATA3) are common immunohistochemical markers used to confirm breast origin. The most widely used of these three markers, GATA3, has the best sensitivity (70–90 %) for all invasive breast cancer (IBCs) and is essential for the differentiation of luminal cells. It is highly expressed in luminal cells but not in basal or myoepithelial cells [3]. Nevertheless, urothelial carcinoma, salivary ductal carcinoma, and numerous other cancers also have GATA3 positivity [4,5].

Sox10 contributes to the development of mammary epithelial cells in vitro, a process mediated by Notch4 and peroxisome-proliferative–activated receptor-binding protein (PBP) in the breast. Multiple studies have shown that SOX10's sensitivity for TNBCs varies from 40 % to 80 % indicating a sensitivity higher than that of GATA3. Recent research has also shown that SOX10 can be highly expressed in TNBCs, but it is typically negative or infrequently positive in ER-positive or HER2-positive breast carcinomas [6,7].

A recently identified marker in the GATA family of zinc finger transcription factors is Trichorhinophalangeal Syndrome Type 1 (TRPS1). Prior research indicates that, in contrast to normal breast cells, TRPS1 is significantly expressed in breast carcinomas [8,9]. Our study intends to thoroughly assess the diagnostic utility of TRPS1, GATA3, and SOX10 immunohistochemical markers in differentiating molecular subtypes of breast cancer within a cohort of 184 patients, as well as investigate their correlations with clinicopathological features.

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