PMID- 36284362 OWN - NLM STAT- MEDLINE DCOM- 20221027 LR - 20231213 IS - 1465-542X (Electronic) IS - 1465-5411 (Print) IS - 1465-5411 (Linking) VI - 24 IP - 1 DP - 2022 Oct 25 TI - Matrix Gla protein (MGP), GATA3, and TRPS1: a novel diagnostic panel to determine breast origin. PG - 70 LID - 10.1186/s13058-022-01569-1 [doi] LID - 70 AB - BACKGROUND: 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). MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. CI - (c) 2022. The Author(s). FAU - Du, Tian AU - Du T AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China. AD - Department of Breast Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. FAU - Pan, Lu AU - Pan L AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China. AD - Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. FAU - Zheng, Chengyou AU - Zheng C AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China. AD - Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. FAU - Chen, Keming AU - Chen K AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China. AD - Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. FAU - Yang, Yuanzhong AU - Yang Y AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China. AD - Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. FAU - Chen, Jiewei AU - Chen J AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China. AD - Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. FAU - Chao, Xue AU - Chao X AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China. AD - Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. FAU - Li, Mei AU - Li M AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China. AD - Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. FAU - Lu, Jiabin AU - Lu J AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China. AD - Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. FAU - Luo, Rongzhen AU - Luo R AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China. AD - Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. FAU - Zhang, Jinhui AU - Zhang J AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China. AD - Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. FAU - Wu, Yu AU - Wu Y AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China. AD - Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. FAU - He, Jiehua AU - He J AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China. hejh@sysucc.org.cn. AD - Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. hejh@sysucc.org.cn. FAU - Jiang, Dongping AU - Jiang D AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China. jiangdp@sysucc.org.cn. AD - Department of Medical Imaging, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. jiangdp@sysucc.org.cn. FAU - Sun, Peng AU - Sun P AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China. sunpeng1@sysucc.org.cn. AD - Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. sunpeng1@sysucc.org.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221025 PL - England TA - Breast Cancer Res JT - Breast cancer research : BCR JID - 100927353 RN - 0 (Biomarkers, Tumor) RN - 0 (GATA3 Transcription Factor) RN - 0 (Mammaglobin A) RN - 0 (Calcium-Binding Proteins) RN - 0 (GATA3 protein, human) RN - 0 (TRPS1 protein, human) RN - 0 (Repressor Proteins) RN - Trichorhinophalangeal Syndrome, Type I SB - IM MH - Female MH - Humans MH - *Triple Negative Breast Neoplasms/diagnosis/genetics/metabolism MH - *Breast Neoplasms/diagnosis/genetics/pathology MH - Biomarkers, Tumor/metabolism MH - GATA3 Transcription Factor/genetics MH - Mammaglobin A/analysis/metabolism MH - Calcium-Binding Proteins MH - Repressor Proteins/genetics/metabolism MH - Matrix Gla Protein PMC - PMC9598034 OTO - NOTNLM OT - Breast carcinoma OT - GATA3 OT - Immunohistochemical OT - MGP OT - TRPS1 COIS- The authors declare that they have no competing interests. EDAT- 2022/10/27 06:00 MHDA- 2022/10/28 06:00 PMCR- 2022/10/25 CRDT- 2022/10/26 00:32 PHST- 2022/05/13 00:00 [received] PHST- 2022/10/18 00:00 [accepted] PHST- 2022/10/26 00:32 [entrez] PHST- 2022/10/27 06:00 [pubmed] PHST- 2022/10/28 06:00 [medline] PHST- 2022/10/25 00:00 [pmc-release] AID - 10.1186/s13058-022-01569-1 [pii] AID - 1569 [pii] AID - 10.1186/s13058-022-01569-1 [doi] PST - epublish SO - Breast Cancer Res. 2022 Oct 25;24(1):70. doi: 10.1186/s13058-022-01569-1.