唾液腺非乳腺样分泌癌中乳腺球蛋白的表达及ETV6基因重排

中国口腔颌面外科杂志 ›› 2016, Vol. 14 ›› Issue (3): 223-227.

唾液腺非乳腺样分泌癌中乳腺球蛋白的表达及ETV6基因重排

孙晶晶, 田臻, 王丽珍, 张春叶, 张莺, 李江

上海交通大学医学院附属第九人民医院·口腔医学院口腔病理科, 上海市口腔医学重点实验室,上海 200011

收稿日期:2016-01-11 出版日期:2016-06-20 发布日期:2016-07-04
通讯作者: 李江,E-mail：lijiang182000@126.com
作者简介:孙晶晶（1989-）,女,在读硕士研究生,E-mail：421214938@qq.com
基金资助:
国家自然科学基金（81372910）; 教育部博士点基金（20120073110084）

Mammaglobin expression and ETV6 gene alteration in salivary non-mammary analogue secretory carcinomas

SUN Jing-jing, TIAN Zhen, WANG Li-zhen, ZHANG Chun-ye, ZHANG Ying, LI Jiang

Department of Oral Pathology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; Shanghai Key Laboratory of Stomatology. Shanghai 200011, China

Received:2016-01-11 Online:2016-06-20 Published:2016-07-04

摘要/Abstract

摘要： 目的分析乳腺球蛋白（mammaglobin,MMG）在唾液腺非乳腺样分泌癌中是否存在表达,以及有表达者是否存在ETV6基因分离,以评价MMG及ETV6基因检测在唾液腺癌病理诊断中的价值。方法选取95例唾液腺非乳腺样分泌癌（包括20例腺泡细胞癌,10例多形性低度恶性腺癌,6例唾液腺导管癌,9例囊腺癌,6例低度恶性筛状囊腺癌,14例黏液表皮样癌,14例恶性多形性腺瘤,16例腺样囊性癌）行MMG免疫组织化学染色,利用荧光原位杂交（FISH）技术进一步分析阳性染色的病例。结果29/95例病例出现MMG阳性表达,其中17例为MMG强阳性,包括4/6例唾液腺导管癌、4/6例低度恶性筛状囊腺癌、4/9例囊腺癌、3/8例恶性多形性腺瘤（腺癌）、1/10例多形性低度恶性腺癌、1/4例高度恶性黏液表皮样癌。全部29例MMG阳性肿瘤经FISH检测,均未发现ETV6基因分离。结论MMG在部分非乳腺样分泌癌中阳性表达,尤其在唾液腺导管癌、低度恶性筛状囊腺癌、囊腺癌中有较高比例的强阳性表达,但MMG阳性表达的非乳腺样分泌癌均不存在ETV6基因分离,提示MMG在鉴别诊断中作用有限,必要时还需辅助分子检测。

关键词: 乳腺球蛋白, 乳腺样分泌癌, 唾液腺肿瘤, ETV6基因重排

Abstract: PURPOSE: To determine the diagnostic value of mammaglobin (MMG) expression and ETV6 gene rearrangement in salivary gland carcinomas in addition to mammary analogue secretory carcinomas (MASC). METHODS: Ninety-five cases of salivary non-MASC carcinomas including 20 acinic cell carcinomas (AciCC), 10 polymorphous low-grade adenocarcinomas (PLGA), 6 salivary ductal carcinomas (SDC), 9 cystadenocarcinomas (CAC), 6 low-grade cribriform cystadenocarcinomas (LGCCC), 14 mucoepidermoid carcinomas (MEC), 14 malignant pleomorphic adenomas (MPA), and 16 adenoid cystic carcinomas (ACC) were selected for MMG immunohistochemical staining, and fluorescence in situ hybridization (FISH) method was further performed in the cases characterized as MMG positive. RESULTS: 29/95 cases showed diffuse or focal staining for MMG and 17 cases demonstrated strong positivity, which included 4/6 SDC, 4/9 CAC, 4/6 LGCCC, 3/8 MPA (adenocarcinoma subtype), 1/10 PLGA and 1/4 high grade MEC. ETV6 gene rearrangement was not detected in any of the 29 MMG-positive cases. CONCLUSIONS: MMG expression was observed in some cases of salivary non-MASC carcinomas, and a higher proportion of strongly positive cases were detected in SDC, LGCCC and CAC, while none of them harbored ETV6 gene rearrangement, indicating that MMG may not serve as a promising diagnostic marker for MASC,and molecular study is needed to distinguish MASC from other salivary gland carcinomas.

Key words: Mammaglobin, Mammary analogue secretory carcinoma, Salivary gland carcinoma, ETV6 gene rearrangement

中图分类号:

R780.2

孙晶晶, 田臻, 王丽珍, 张春叶, 张莺, 李江. 唾液腺非乳腺样分泌癌中乳腺球蛋白的表达及ETV6基因重排[J]. 中国口腔颌面外科杂志, 2016, 14(3): 223-227.

SUN Jing-jing, TIAN Zhen, WANG Li-zhen, ZHANG Chun-ye, ZHANG Ying, LI Jiang. Mammaglobin expression and ETV6 gene alteration in salivary non-mammary analogue secretory carcinomas[J]. China J Oral Maxillofac Surg, 2016, 14(3): 223-227.

参考文献

[1] Chiosea SI, Griffith C, Assaad A, et al. Clinicopathological characterization of mammary analogue secretory carcinoma of salivary glands[J]. Histopathology, 2012, 61(3): 387-394.
[2] Sk&#x0dbc0;&#x0dd61;lov&#x0dbc0;&#x0dd61; A, Vanecek T, Sima R, et al. Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity [J]. Am J Surg Pathol, 2010, 34(5): 599-608.
[3] Higuchi K, Urano M, Takahashi RH, et al. Cytological features of mammary analogue secretory carcinoma of salivary gland: fine-needle aspiration of seven cases [J]. Diagn Cytopathol, 2014, 42(10): 846-855.
[4] Bishop JA, Yonescu R, Batista D, et al. Most non-parotid "acini ccell carcinomas" represent mammary analog secretory carcinomas [J]. Am J Surg Pathol, 2013, 37(7): 1053-1057.
[5] Mariano FV, dos Santos HT, Azañero WD, et al. Mammary analogue secretory carcinoma of salivary glands is a lipid-rich tumour, and adipophilin can be valuable in its identification [J]. Histopathology, 2013, 63(4): 558-567.
[6] Bishop JA, Yonescu R, Batista D, et al. Utility of mammaglobin immunohistochemistry as a proxy marker for the ETV6-NTRK3 translocation in the diagnosis of salivary mammary analogue secretory carcinoma [J]. Hum Pathol, 2013, 44(10): 1982-1988.
[7] Patel KR, Solomon IH, El-Mofty SK, et al. Mammaglobin and S-100 immunoreactivity in salivary gland carcinomas other than mammary analogue secretory carcinoma [J]. Hum Pathol, 2013, 4(11): 2501-2508.
[8] Thompson L. World Health Organization classification of tumours: pathology and genetics of head and neck tumours [J]. Ear Nose Throat J, 2006, 85(2): 74.
[9] Skálová A, Vanecek T, Simpson RH, et al. Mammary analogue secretory carcinoma of salivary glands: molecular analysis of 25 ETV6 gene rearranged tumors with lack of detection of classical ETV6-NTRK3 fusion transcript by standard RT-PCR: report of 4 cases harboring ETV6-X gene fusion [J]. Am J Surg Pathol, 2016, 40(1): 3-13.
[10] Serrano-Arévalo ML, Mosqueda-Taylor A, Domínguez-Malagón H, et al. Mammary analogue secretory carcinoma (MASC) of salivary gland in four Mexican patients [J]. Med Oral Patol Oral Cir Bucal, 2015, 20(1): e23-29.
[11] Kawahara A, Taira T, Abe H, et al. Diagnostic utility of phosphorylated signal transducer and activator of transcription 5 immunostaining in the diagnosis of mammary analogue secretory carcinoma of the salivary gland: a comparative study of salivary gland cancers [J]. Cancer Cytopathol, 2015, 123(10): 603-611.
[12] Sasaki E, Tsunoda N, Hatanaka Y, et al. Breast-specific expression of MGB1/mammaglobin: an examination of 480 tumors from various organs and clinicopathological analysis of MGB1-positive breast cancers [J]. Mod Pathol, 2007, 20(2): 208-214.
[13] Bhargava R, Beriwal S, Dabbs DJ. Mammaglobin vs GCDFP-15: an immunohistologic validation survey for sensitivity and specificity [J]. Am J Clin Pathol, 2007, 127(1): 103-113.
[14] Connor A, Perez-Ordoñez B, Shago M, et al. Mammary analog secretory carcinoma of salivary gland origin with the ETV6 gene rearrangement by FISH: expanded morphologic and immunohistochemical spectrum of a recently described entity [J]. Am J Surg Pathol, 2012, 36(1): 27-34.
[15] Laco J, Švajdler M Jr, Andrejs J, et al. Mammary analog secretory carcinoma of salivary glands: a report of 2 cases with expression of basal/myoepithelial markers (calponin, CD10 and p63 protein) [J]. Pathol Res Pract, 2013, 209(3): 168-172.
[16] Fehr A, Löning T, Stenman G. Mammary analogue secretory carcinoma of the salivary glands with ETV6-NTRK3 gene fusion [J]. Am J Surg Pathol, 2011, 35(10): 1600-1602.
[17] Pisharodi L. Mammary analog secretory carcinoma of salivary gland: cytologic diagnosis and differential diagnosis of an unreported entity [J]. Diagn Cytopathol, 2013, 41(3): 239-241.
[18] Urano M, Nagao T, Miyabe S, et al. Characterization of mammary analogue secretory carcinoma of the salivary gland: discrimination from its mimics by the presence of the ETV6-NTRK3 translocation and novel surrogate markers [J]. Hum Pathol, 2015, 46(1): 94-103.
[19] Williams L, Chiosea SI. Mammary analogue secretory carcinoma mimicking salivary adenoma [J]. Head Neck Pathol, 2013, 7(4): 316-319.