Using bioinformatics analyses, we identified a potential diagnostic panel to determine breast origin: matrix Gla protein (MGP), transcriptional repressor GATA binding 1 (TRPS1), and GATA-binding protein 3 (GATA3). We compared MGP, TRPS1, and GATA3 expression in different subtypes of breast carcinoma of (n = 1201) using IHC. As a newly identified marker, MGP expression was also evaluated in solid tumors (n = 2384) and normal tissues (n = 1351) from different organs.
MGP and TRPS1 had comparable positive expression in HER2-positive (91.2% vs. 92.0%, p = 0.79) and TNBC subtypes (87.3% vs. 91.2%, p = 0.18). GATA3 expression was lower than MGP (p < 0.001) or TRPS1 (p < 0.001), especially in HER2-positive (77.0%, p < 0.001) and TNBC (43.3%, p < 0.001) subtypes. TRPS1 had the highest positivity rate (97.9%) in metaplastic TNBCs, followed by MGP (88.6%), while only 47.1% of metaplastic TNBCs were positive for GATA3. When using MGP, GATA3, and TRPS1 as a novel IHC panel, 93.0% of breast carcinomas were positive for at least two markers, and only 9 cases were negative for all three markers. MGP was detected in 36 cases (3.0%) that were negative for both GATA3 and TRPS1. MGP showed mild-to-moderate positive expression in normal hepatocytes, renal tubules, as well as 31.1% (99/318) of hepatocellular carcinomas. Rare cases (0.6-5%) had focal MGP expression in renal, ovarian, lung, urothelial, and cholangiocarcinomas.
Our findings suggest that MGP is a newly identified sensitive IHC marker to support breast origin. MGP, TRPS1, and GATA3 could be applied as a reliable diagnostic panel to determine breast origin in clinical practice.
使用生物信息学分析,我们确定了一个潜在的诊断小组来确定乳腺来源:基质Gla蛋白(MGP),转录阻遏物GATA结合1(TRPS1),和GATA结合蛋白3(GATA3)。我们比较了MGP,运用IHC法检测TRPS1和GATA3在分歧亚型乳腺癌(n=1201)中的表达。作为一个新发现的标记,还在来自不同器官的实体瘤(n=2384)和正常组织(n=1351)中评估MGP表达。
MGP和TRPS1在HER2阳性中具有相当的阳性表达(91.2%vs.92.0%,p=0.79)和TNBC亚型(87.3%vs.91.2%,p=0.18)。GATA3表达低于MGP(p<0.001)或TRPS1(p<0.001),尤其是HER2阳性(77.0%,p<0.001)和TNBC(43.3%,p<0.001)亚型。TRPS1在化生TNBC中的阳性率最高(97.9%),其次是MGP(88.6%),而只有47.1%的化生TNBC对GATA3呈阳性。使用MGP时,GATA3和TRPS1作为一个新颖的IHC面板,93.0%的乳腺癌对至少两个标志物呈阳性,只有9例3种标志物均为阴性。36例(3.0%)检测到MGP,GATA3和TRPS1均为阴性。MGP在正常肝细胞中呈轻度至中度阳性表达,肾小管,以及31.1%(99/318)的肝细胞癌。罕见病例(0.6-5%)在肾脏中有局灶性MGP表达,卵巢,肺,尿路上皮,和胆管癌.
我们的研究结果表明,MGP是一种新发现的支持乳腺来源的敏感IHC标记。MGP,TRPS1和GATA3可以用作可靠的诊断小组,以确定临床实践中的乳腺起源。