乳腺腺样囊性癌相关分子标志物的研究进展

doi:10.3877/cma.j.issn.1674-0793.2019.01.014

乳腺腺样囊性癌（ACC）是浸润性乳腺癌的一种罕见亚型，近年来关于乳腺ACC分子标志物的研究取得了一些进展，这为其防治打下一定基础。研究发现MYB-NFIB融合基因在ACC中特异性出现，MYB-NFIB融合基因和（或）MYB与乳腺ACC的发生发展密切相关。此外，部分乳腺ACC中表皮生长因子受体（EGFR）过表达，提示抗EGFR靶向治疗可能在乳腺ACC中存在良好的疗效。人第10号染色体缺失的磷酸酶及张力蛋白同源基因和磷脂酰肌醇激酶3催化亚基α基因的共存突变可能与乳腺ACC的转移相关。雌激素受体亚型α36在部分乳腺ACC中表达，提示抗雌激素疗法对乳腺ACC患者可能有效。部分乳腺ACC过表达胰岛素样生长因子Ⅱ mRNA结合蛋白3，且其过表达强度可能与其转移性等预后因素有关。乳腺ACC中组蛋白甲基转移酶2（EZH2）表达水平与Ki-67正相关，并与转移表现出相关性，EZH2可能成为判断乳腺ACC预后、指导手术范围的重要指标。乳腺ACC中DNA拓扑异构酶Ⅱα基因不表达或弱表达，提示蒽环类的化学疗法似乎对乳腺ACC患者无效。

关键词: 癌，腺样囊性, 受体，表皮生长因子, 分子靶向治疗, MYB-NFIB

Adenoid cystic carcinoma (ACC) of the breast is a rare subtype of invasive breast cancer. In recent years, some progress has been made in the study of ACC of the breast molecular markers, which lays foundation for the prevention and treatment of ACC of the breast. The MYB-NFIB fusion gene is specifically found in adenoid cystic carcinoma, and the MYB-NFIB fusion gene and/or MYB are closely related to the development of ACC of the breast. In addition, overexpression of epidermal growth factor receptor (EGFR) in ACC of the breast suggests that anti-EGFR targeted therapy may have good effect in ACC of the breast. Coexisting mutations in phosphatase and tensin homolog deleted on chromosome ten and phosphoinositide-3-kinase catalytic alpha polypeptide gene may be associated with metastasis of ACC of the breast. Estrogen receptor-α36 is expressed in some cases of ACC of the breast, suggesting that anti-estrogen therapy may be effective in ACC of the breast patients. Part of ACC of the breast overexpresses insulin-like growth factor-Ⅱ mRNA-binding protein 3, and its overexpression intensity may be related to prognostic factors such as metastasis. The expression level of enhancer of zeste homolog 2 (EZH2) in ACC of the breast was positively correlated with Ki-67 and correlated with metastasis. EZH2 may be an important indicator to judge the prognosis of ACC of the breast and guide the scope of surgery. Topoisomerase Ⅱα in ACC of the breast is not expressed or weakly expressed, suggesting that anthracycline chemotherapy appears to be ineffective in ACC of the breast patients.

Key words: Carcinoma, adenoid cystic, Receptor, epidermal growth factor, Molecular targeted therapy, MYB-NFIB

表1 MYB-NFIB融合基因及其转录产物在乳腺ACC中检出情况表（%）

作者及年份	FISH检测	RT-PCR检测
Persson等2009^[12]	-	100.0(4/4)
Brill等2011^[14]	-	50.0(2/4)
Wetterskog等2012^[16]	92.3(12/13)	30.8(4/13)
Hudson等2014^[17]	0(0/1)	-
D'Alfonso等2014^[18]	-	20.1(6/29)
Martelotto等2015^[10]	-	83.3(10/12)
李丽2017^[15]	-	31.6(6/19)
合计	85.7(12/14)	39.5(32/81)

表1 MYB-NFIB融合基因及其转录产物在乳腺ACC中检出情况表（%）

作者及年份	FISH检测	RT-PCR检测
Persson等2009^[12]	-	100.0(4/4)
Brill等2011^[14]	-	50.0(2/4)
Wetterskog等2012^[16]	92.3(12/13)	30.8(4/13)
Hudson等2014^[17]	0(0/1)	-
D'Alfonso等2014^[18]	-	20.1(6/29)
Martelotto等2015^[10]	-	83.3(10/12)
李丽2017^[15]	-	31.6(6/19)
合计	85.7(12/14)	39.5(32/81)

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Research progress of molecular markers related to adenoid cystic carcinoma of the breast

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Research progress of molecular markers related to adenoid cystic carcinoma of the breast