الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
According to the latest global cancer statistics 2020, female breast cancer has become the most commonly diagnosed tumor, with an estimated 2.3 million new cases (11.7% of total cases) and 0.68 million deaths (6.9% of total cases). On the basis of specific receptors: estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 proliferative index, breast cancer can be divided into four clinical subtypes, luminal A, luminal B, HER2-positive, and triple-negative molecular subtype which is the most aggressive phenotype and overlaps with basal-type breast cancer. GATA-binding protein 3 (GATA3), gross cystic disease fluid protein 15 (GCDFP15), and mammaglobin are routinely used immunohistochemical markers to support breast origin. Among these three markers, GATA3 is the most widely used and has the highest sensitivity for all IBCs. It is critical for luminal cell differentiation and often expressed in luminal cells but not basal/myoepithelial cells. However, GATA3 is also positive in urothelial carcinoma, salivary ductal carcinoma, and many other tumors. Furthermore, the expression of all three markers is significantly reduced in TNBCs, with a range of 20%-60%, compared to ER-positive or HER2-positive breast cancers; therefore, new breast markers with higher sensitivity for TNBC are much needed. Recently, TRPS1 (trichorhinophalangeal syndrome type 1) has been identified as a novel GATA transcription factor, functioning as an essential regulator for the growth and differentiation of normal mammary epithelial cells and involved in the development of BC. It is also a critical activator of mesenchymal-to-epithelial transition during embryonic development in several tissues, including bone, cartilage, and kidney. This study investigated the immunohistochemical expression of TRPS1 and GATA3 in breast and non-breast carcinomas. As well as, the relations between TRPS1 and GATA3 expression with clinicopathologic characteristics in breast carcinoma was examined. Immunohistochemical staining with TRPS1 and GATA3 were carried out on 70 primary breast carcinoma specimens, and 80 non-breast carcinoma specimens. TRPS1 was detected as a brownish nuclear staining in 65 (92.9%) BC specimens and only in three (3.7%) non-breast carcinoma specimens. TRPS1 provided 92.9% sensitivity, 96.3% specificity, and 0.974 area under curve (AUC) with significant value (P <0.001). TRPS1 had 95.6% positive predictive value (PPV), 93.9% negative predictive value (NPV) and a diagnostic accuracy of 94.7%. The optimal TRPS1 cut-off value that afforded the highest sensitivity and specificity for distinguishing breast from nonbreast origin was 12%. Regarding the molecular subtypes of the studied BC cases, TRPS1 showed positivity in 100% of luminal subtype, 82.4% of HER2 enriched subtype, and 86.7% of triple negative breast carcinoma. Considering the validity of TRPS1 and GATA3 individually, this study achieved that TRPS1 was more sensitive and specific than GATA3 especially in TNBC (86.7% versus 26.7%). Combination of TRPS1and GATA3 offered higher sensitivity and specificity 94.3% and 100% respectively. As regards the relations of TRPS1 and GATA3 with clinicopathological characteristics, it was noticed that high TRPS1 and GATA3 expression were statistically associated with low-grade breast carcinoma, absent vascular, perineural, skin and nipple invasion invasion and absent or lesser degree lymph node metastasis. Moreover, higher expression of both markers were detected in hormone responsive tumors than HER2 enriched and TNBC. This denoted that high TRPS1 and GATA3 expression can be related to well differentiated and less invasive tumors and subsequently associated with better prognosis.