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Abstract：
Metastatic breast carcinoma is commonly considered during differential diagnosis when metastatic disease is detected in females. In addition to the tumor morphology and documented clinical history, sensitive and specific immunohistochemical (IHC) markers such as GCDFP-15, mammaglobin, and GATA3 are helpful for determining breast origin. However, these markers are reported to show lower sensitivity in certain subtypes, such as triple-negative breast cancer (TNBC).
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.
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.
摘要：
当在女性中检测到转移性疾病时，通常在鉴别诊断期间考虑转移性乳腺癌。除了肿瘤形态和有记录的临床病史，敏感和特异性的免疫组织化学（IHC）标记，如GCDFP-15，乳腺球蛋白，和GATA3有助于确定乳腺来源。然而,据报道，这些标记在某些亚型中显示出较低的敏感性，例如三阴性乳腺癌（TNBC）。
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。
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。
