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微纤维相关蛋白5(MFAP5)在非特殊类型浸润性乳腺癌中的免疫组化表达

Immunohistochemical Expression of Microfibrillar-associated Protein 5 (MFAP5) in Invasive Breast Carcinoma of No Special Type.

作者信息

Dawoud Marwa M, Abouelfadl Dalia, Abdou Asmaa G, Elkhouly Enas A B

机构信息

Departments of Pathology.

Department of Pathology, Medical Research Division, National Research Center, Egypt.

出版信息

Appl Immunohistochem Mol Morphol. 2019 Oct;27(9):649-657. doi: 10.1097/PAI.0000000000000686.

DOI:10.1097/PAI.0000000000000686
PMID:30320661
Abstract

Breast cancer (BC) remains the most prevalent female cancer in Egypt and worldwide. Microfibrillar-associated protein 5 (MFAP5) is a multifunctional glycoprotein. Although MFAP5 gene was among the genes that found globally expressed in human cancers, it had been only recently reported in few cancer research studies. This is a retrospective study that has been conducted on 66 Egyptian patients who had invasive carcinoma of no special type. Immunohistochemical staining for MFAP5 was applied on the archival formalin-fixed paraffin-embedded blocks. Staining was assessed semiquantitatively and correlated with the available clinicopathologic parameters and immunohistochemical subtypes of BC. MFAP5 epithelial cytoplasmic expression was observed in 89.4% (59/66) of cases. In contrast, nuclear expression was seen in non-neoplastic breast lobules and premalignant lesions adjacent to tumors that also exhibited constant staining in myoepithelial layer. Statistical analysis of epithelial cytoplasmic expression revealed association of MFAP5 expression with tumor size (P=0.046), high histologic grade (P=0.007), presence of lymph node metastasis (P=0.014), poor Nottingham Prognostic Index (NPI) (P=0.001), late stage (P=0.008), immunohistochemical subtypes of BC (P=0.018), and increased microvessel density using CD34 immunostianing (P=0.04). MFAP5 cytoplasmic expression was also observed in an adjacent duct carcinoma in situ component in 37/45 cases (82.2%). This study showed that MFAP5 is a novel myoepithelial cell marker that appears to be upregulated in duct epithelium in duct carcinoma in situ and invasive carcinoma of no special type during tumorogenesis and that its cytoplasmic expression in invasive tumors seems to have a poor prognostic role manifested by its association with poor prognostic parameters such as high grade, late stage, lymph node invasion, and increased microvessel density.

摘要

乳腺癌(BC)仍是埃及和全球最常见的女性癌症。微原纤维相关蛋白5(MFAP5)是一种多功能糖蛋白。尽管MFAP5基因是在全球人类癌症中均有表达的基因之一,但直到最近才在少数癌症研究中被报道。这是一项对66例非特殊类型浸润性癌的埃及患者进行的回顾性研究。对存档的福尔马林固定石蜡包埋块进行MFAP5免疫组织化学染色。对染色进行半定量评估,并与现有的临床病理参数和乳腺癌免疫组织化学亚型相关联。在89.4%(59/66)的病例中观察到MFAP5上皮细胞质表达。相比之下,在非肿瘤性乳腺小叶和肿瘤旁的癌前病变中可见核表达,肌上皮层也呈现持续染色。上皮细胞质表达的统计分析显示,MFAP5表达与肿瘤大小(P=0.046)、高组织学分级(P=0.007)、淋巴结转移的存在(P=0.014)、不良诺丁汉预后指数(NPI)(P=0.001)、晚期(P=0.008)、乳腺癌免疫组织化学亚型(P=0.018)以及使用CD34免疫染色检测到的微血管密度增加(P=0.04)相关。在37/45例(82.2%)病例的相邻原位导管癌成分中也观察到MFAP5细胞质表达。本研究表明,MFAP5是一种新的肌上皮细胞标志物,在原位导管癌和非特殊类型浸润性癌的肿瘤发生过程中,导管上皮中似乎上调,并且其在浸润性肿瘤中的细胞质表达似乎具有不良预后作用,表现为与高分级、晚期、淋巴结浸润和微血管密度增加等不良预后参数相关。

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Hypoxia-induced MFAP5 Promotes Tumor Migration and Invasion via AKT Pathway in Head and Neck Squamous Cell Carcinoma.缺氧诱导的MFAP5通过AKT通路促进头颈部鳞状细胞癌的肿瘤迁移和侵袭。
J Cancer. 2020 Jan 14;11(6):1596-1605. doi: 10.7150/jca.38217. eCollection 2020.
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Stromal fibroblast-derived MFAP5 promotes the invasion and migration of breast cancer cells via Notch1/slug signaling.基质成纤维细胞衍生的MFAP5通过Notch1/蛞蝓信号通路促进乳腺癌细胞的侵袭和迁移。
Clin Transl Oncol. 2020 Apr;22(4):522-531. doi: 10.1007/s12094-019-02156-1. Epub 2019 Jun 12.