唾液腺癌分子病理诊断进展

doi:10.3969/j.issn.1005-4979.2020.06.001

《口腔颌面外科杂志》 ›› 2020, Vol. 30 ›› Issue (6): 341-347. doi: 10.3969/j.issn.1005-4979.2020.06.001

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唾液腺癌分子病理诊断进展

夏荣辉(), 李江^*()

上海交通大学医学院附属第九人民医院口腔病理科，上海 200011

收稿日期:2020-10-27 修回日期:2020-11-16 出版日期:2020-12-28 发布日期:2024-03-20
通讯作者: 李江，教授. E-mail: lijiang182000@126.com

作者简介:

夏荣辉（1985—），男，福建人，主治医师，博士. E-mail: xrh335@163.com

[专家介绍] 李江，教授、主任医师，博士研究生导师，上海交通大学医学院附属第九人民医院口腔病理科主任。中华口腔医学会口腔病理专业委员会副主任委员，中华医学会病理分会头颈组副组长，国家医学资格考试口腔组织病理组组长，上海市口腔医学会口腔基础医学分会主任委员，WHO头颈肿瘤分类（2017版）参编者。人民卫生出版社规划教材《口腔组织病理学》（2020版）副主编，中华口腔医学会《口腔癌及口咽癌病理诊断规范》《唾液腺肿瘤病理诊断规范》首席专家，《中华口腔医学杂志》《华西口腔医学杂志》《口腔颌面外科杂志》《上海口腔医学》等杂志编委，Oral Oncology、Int J Oral Maxillofac Surg、Triple O等杂志审稿者。具有扎实的口腔病理专业基础知识和丰富的临床病理诊断经验。科研重点为唾液腺肿瘤病理及发生机制的研究，主持包括5项国家自然科学基金项目在内的科研项目20余项，以第一作者及通信作者发表SCI收录论文40余篇。

基金资助:
国家自然科学基金项目(81872187); 国家自然科学基金项目(81702694)

Advances in Molecular Pathological Diagnosis of Salivary Gland Carcinomas

XIA Ronghui(), LI Jiang^*()

Department of Oral Pathology, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, China

Received:2020-10-27 Revised:2020-11-16 Online:2020-12-28 Published:2024-03-20

摘要/Abstract

摘要：

近年来唾液腺癌的分子检测取得了巨大的进展，越来越多的遗传学改变被发现。这些遗传学改变对唾液腺癌的病理诊断起了重要的辅助作用，也对唾液腺癌的命名、分类及新类型肿瘤的发现产生着影响。本文对近年来发现的唾液腺癌中重要遗传学改变及部分肿瘤中相应蛋白的表达变化进行介绍，这些变化在相关肿瘤的病理诊断、预后评估、靶向治疗中都发挥着重要的作用。

关键词: 唾液腺癌, 融合基因, 突变

Abstract:

In recent years, great progress has been achieved in molecular detection of salivary gland carcinomas, and more and more genetic changes have been found. These genetic changes play an important role in the pathological diagnosis of salivary gland carcinomas, and also have an impact on the naming, classification and discovery of new types of salivary gland carcinomas. In this review, we will introduce the important genetic alterations in salivary gland carcinomas and the changes of corresponding protein expression in some tumors. These changes play an important role in the pathological diagnosis, prognosis evaluation and targeted treatment of the related carcinomas.

Key words: salivary gland carcinoma, fusion gene, mutation

夏荣辉, 李江. 唾液腺癌分子病理诊断进展[J]. 《口腔颌面外科杂志》, 2020, 30(6): 341-347.

XIA Ronghui, LI Jiang. Advances in Molecular Pathological Diagnosis of Salivary Gland Carcinomas[J]. 《Journal of Oral and Maxillofacial Surgery》, 2020, 30(6): 341-347.

https://journal06.magtech.org.cn/Jweb_joms/CN/Y2020/V30/I6/341

图/表 7

图1 腺样囊性癌组织学表现、MYB蛋白表达和MYB基因分离探针FISH检测注：A. 腺样囊性癌中典型的筛状结构，可见个别腺管结构（HE, ×100），右下角插图显示FISH检测MYB基因断裂（×1 000）；B. 大部分肿瘤细胞核表达MYB蛋白（IHC, ×200）。

Figure 1 The histological features, MYB expression and FISH detection of MYB gene rearrangement of adenoid cystic carcinoma

图2 黏液表皮样癌组织学表现、阿辛蓝染色和MAML2基因分离探针FISH检测注：A. 黏液表皮样癌中可见囊腔形成，腔面可见较多黏液细胞（HE, ×100），右下角插图显示FISH检测MAML2基因断裂（×1 000）；B. 黏液细胞阿辛蓝染色阳性（IHC, ×200）。

Figure 2 The histological features, Alcian blue staining and FISH detection of MAML2 gene rearrangement of mucoepidermoid carcinoma

图3 分泌性癌组织学表现、Pan-Trk蛋白表达和ETV6基因分离探针FISH检测注：A. 分泌性癌中可见肿瘤细胞排列呈微囊状，胞质嗜酸性（HE, ×100），右下角插图显示FISH检测ETV6基因断裂（×1 000）；B. Pan-Trk蛋白免疫组化染色可见大部分细胞呈核阳性（IHC, ×200）。

Figure 3 The histological features, Pan-Trk expression and FISH detection of ETV6 gene rearrangement of secretory carcinoma

图4 唾液腺透明细胞癌组织学表现、CK7蛋白表达和EWSR1-ATF1融合探针FISH检测注：A. 透明细胞癌中，肿瘤细胞呈片状、巢状排列，部分细胞胞质透明（HE, ×100），右下角插图显示FISH检测EWSR1-ATF1基因融合（×1 000）；B. 大部分细胞表达CK7蛋白（IHC, ×200）。

Figure 4 The histological features, CK7 expression and FISH detection of EWSR1-ATF1 fusion of salivary clear cell carcinoma

图5 腺泡细胞癌组织学表现、NR4A3蛋白表达和NR4A3基因分离探针FISH检测注：A. 腺泡细胞癌中肿瘤细胞胞质含大量嗜碱性颗粒，肿瘤细胞为特征性的腺泡样细胞（HE, ×100），右下角插图显示FISH检测NR4A3基因断裂（×1 000）；B. 大部分肿瘤细胞核弥漫表达NR4A3蛋白（IHC, ×200）。

Figure 5 The histological features, NR4A3 expression and FISH detection of NR4A3 gene rearrangement of acinic cell carcinoma

图6 NUT癌组织学表现、NUT蛋白表达和NUT基因分离探针FISH检测注：A. NUT癌肿瘤细胞排列呈条索状、片状，胞质淡嗜酸性染色或透明（HE, ×100），右下角插图显示FISH检测NUT基因断裂（×1 000）；B. 大部分肿瘤细胞核表达NUT蛋白（IHC, ×200）。

Figure 6 The histological features, NUT expression and FISH detection of NUT gene rearrangement of NUT carcinoma

图7 造釉细胞瘤样尤文肉瘤组织学表现、NKX2.2蛋白表达和EWSR1-FLI1融合基因探针FISH检测注：A. 造釉细胞瘤样尤文肉瘤肿瘤细胞呈巢状、分叶状排列，周边细胞略呈栅栏状（HE, ×100），右下角插图显示FISH检测EWSR1-FLI1基因融合（×1 000）；B. NKX2.2蛋白在大部分肿瘤细胞核中弥漫强阳性表达（IHC, ×200）。

Figure 7 The histological features, NKX2.2 expression and FISH detection of EWSR1-FLI1 fusion of adamantinoma-like Ewing sarcoma

参考文献 38

[1]	El-Naggar AK, Chan JKC, Grandis JR, et al. WHO classification of head and neck[M]. 2017, International Agency for Research on Cancer, 2017: 159-183.
[2]	Skálová A, Stenman G, Simpson RHW, et al. The role of molecular testing in the differential diagnosis of salivary gland carcinomas[J]. Am J Surg Pathol, 2018, 42(2): e11-e27. doi: 10.1097/PAS.0000000000000980 URL
[3]	Persson M, Andrén Y, Mark J, et al. Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck[J]. Proc Natl Acad Sci USA, 2009, 106(44):18740-18744. doi: 10.1073/pnas.0909114106 pmid: 19841262
[4]	Han J, Zhang CY, Gu T, et al. Analysis of clinicopathological characteristics, MYB rearrangement and prognostic factors in salivary adenoid cystic carcinoma[J]. Oncol Lett, 2019, 17(3): 2915-2922.
[5]	Togashi Y, Dobashi A, Sakata S, et al. MYB and MYBL1 in adenoid cystic carcinoma: diversity in the mode of genomic rearrangement and transcripts[J]. Mod Pathol, 2018, 31(6): 934-946. doi: 10.1038/s41379-018-0008-8 URL
[6]	Brayer KJ, Frerich CA, Kang HN, et al. Recurrent fusions in MYB and MYBL1 define a common, transcription factor-driven oncogenic pathway in salivary gland adenoid cystic carcinoma[J]. Cancer Discov, 2016, 6(2): 176-187. doi: 10.1158/2159-8290.CD-15-0859 pmid: 26631070
[7]	Mitani Y, Liu B, Rao PH, et al. Novel MYBL1 gene rearrangements with recurrent MYBL1-NFIB fusions in salivary adenoid cystic carcinomas lacking t(6;9) translocations[J]. Clin Cancer Res, 2016, 22(3): 725-733. doi: 10.1158/1078-0432.CCR-15-2867-T pmid: 26631609
[8]	Ho AS, Ochoa A, Jayakumaran G, et al. Genetic hallmarks of recurrent/metastatic adenoid cystic carcinoma[J]. J Clin Invest, 2019, 129(10): 4276-4289. doi: 10.1172/JCI128227 pmid: 31483290
[9]	Kang H, Tan M, Bishop JA, et al. Whole-exome sequencing of salivary gland mucoepidermoid carcinoma[J]. Clin Cancer Res, 2017, 23(1): 283-288. doi: 10.1158/1078-0432.CCR-16-0720 pmid: 27340278
[10]	Bishop JA, Cowan ML, Shum CH, et al. MAML2 rearrangements in variant forms of mucoepidermoid carcinoma: Ancillary diagnostic testing for the ciliated and Warthin-like variants[J]. Am J Surg Pathol, 2018, 42(1): 130-136. doi: 10.1097/PAS.0000000000000932 pmid: 28877061
[11]	Bell D, Ferrarotto R, Liang L, et al. Pan-Trk immunohistochemistry reliably identifies ETV6-NTRK3 fusion in secretory carcinoma of the salivary gland[J]. Virchows Arch, 2020, 476(2): 295-305. doi: 10.1007/s00428-019-02640-7
[12]	Rooper LM, Karantanos T, Ning Y, et al. Salivary secretory carcinoma with a novel ETV6-MET fusion: expanding the molecular spectrum of a recently described entity[J]. Am J Surg Pathol, 2018, 42(8): 1121-1126. doi: 10.1097/PAS.0000000000001065 pmid: 29683815
[13]	Black M, Liu CZ, Onozato M, et al. Concurrent identification of novel EGFR-SEPT14 fusion and ETV6-RET fusion in secretory carcinoma of the salivary gland[J]. Head Neck Pathol, 2020, 14(3): 817-821. doi: 10.1007/s12105-019-01074-6 pmid: 31502214
[14]	Guilmette J, Dias-Santagata D, Nosé V, et al. Novel gene fusions in secretory carcinoma of the salivary glands: Enlarging the ETV6 family[J]. Hum Pathol, 2019, 83: 50-58. doi: S0046-8177(18)30316-2 pmid: 30130630
[15]	Skálová A, Banečkova M, Thompson LDR, et al. Expanding the molecular spectrum of secretory carcinoma of salivary glands with a novel VIM-RET fusion[J]. Am J Surg Pathol, 2020, 44(10): 1295-1307. doi: 10.1097/PAS.0000000000001535 pmid: 32675658
[16]	Sasaki E, Masago K, Fujita S, et al. Salivary secretory carcinoma harboring a novel ALK fusion: Expanding the molecular characterization of carcinomas beyond the ETV6 gene[J]. Am J Surg Pathol, 2020, 44(7): 962-969. doi: 10.1097/PAS.0000000000001471 pmid: 32205481
[17]	Sun JJ, Wang LZ, Tian Z, et al. Higher Ki67 index, nodal involvement, and invasive growth were high risk factors for worse prognosis in conventional mammary analogue secretory carcinom[J]. J Oral Maxillofac Surg, 2019, 77(6): 1187-1202. doi: 10.1016/j.joms.2019.01.002 URL
[18]	Drilon A, Laetsch TW, Kummar S, et al. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children[J]. N Engl J Med, 2018, 378(8): 731-739. doi: 10.1056/NEJMoa1714448 URL
[19]	Laetsch TW, DuBois SG, Mascarenhas L, et al. Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study[J]. Lancet Oncol, 2018, 19(5): 705-714. doi: S1470-2045(18)30119-0 pmid: 29606586
[20]	Liu DZ, Offin M, Harnicar S, et al. Entrectinib: an orally available, selective tyrosine kinase inhibitor for the treatment of NTRK, ROS1, and ALK fusion-positive solid tumors[J]. Ther Clin Risk Manag, 2018, 14: 1247-1252. doi: 10.2147/TCRM URL
[21]	Hsieh MS, Wang H, Lee YH, et al. Reevaluation of MAML2 fusion-negative mucoepidermoid carcinoma: a subgroup being actually hyalinizing clear cell carcinoma of the salivary gland with EWSR1 translocation[J]. Hum Pathol, 2017, 61: 9-18. doi: 10.1016/j.humpath.2016.06.029 URL
[22]	Sebastiao APM, Xu B, Lozada JR, et al. Histologic spectrum of polymorphous adenocarcinoma of the salivary gland harbor genetic alterations affecting PRKD genes[J]. Mod Pathol, 2020, 33(1): 65-73. doi: 10.1038/s41379-019-0351-4 URL
[23]	Skálová A, Gnepp DR, Lewis JS Jr, et al. Newly described entities in salivary gland pathology[J]. Am J Surg Pathol, 2017, 41(8): e33-e47. doi: 10.1097/PAS.0000000000000883 URL
[24]	Palicelli A. Intraductal carcinomas of the salivary glands: Systematic review and classification of 93 published cases[J]. APMIS, 2020, 128(3): 191-200. doi: 10.1111/apm.13009 pmid: 31697865
[25]	Skálová A, Vanecek T, Uro-Coste E, et al. Molecular profiling of salivary gland intraductal carcinoma revealed a subset of tumors harboring NCOA4-RET and novel TRIM27-RET fusions: a report of 17 cases[J]. Am J Surg Pathol, 2018, 42(11):1445-1455. doi: 10.1097/PAS.0000000000001133 pmid: 30045065
[26]	Skálová A, Ptáková N, Santana T, et al. NCOA4-RET and TRIM27-RET are characteristic gene fusions in salivary intraductal carcinoma, including invasive and metastatic tumors: is "intraductal" correct[J]. Am J Surg Pathol, 2019, 43(10):1303-1313. doi: 10.1097/PAS.0000000000001301 pmid: 31162284
[27]	Lu H, Graham RP, Seethala R, et al. Intraductal carcinoma of salivary glands harboring TRIM27-RET fusion with mixed low grade and apocrine types[J]. Head Neck Pathol. 2020, 14(1):239-245. doi: 10.1007/s12105-018-0996-1 pmid: 30610524
[28]	Weinreb I, Bishop JA, Chiosea SI, et al. Recurrent RET gene rearrangements in intraductal carcinomas of salivary gland[J]. Am J Surg Pathol, 2018, 42(4): 442-452. doi: 10.1097/PAS.0000000000000952 pmid: 29443014
[29]	Rooper LM, Thompson LDR, Gagan J, et al. Salivary intraductal carcinoma arising within intraparotid lymph node: A report of 4 cases with identification of a novel STRN-ALK fusion[J]. Head Neck Pathol, 2020.
[30]	Bishop JA, Gagan J, Krane JF, et al. Low-grade apocrine intraductal carcinoma: expanding the morphologic and molecular spectrum of an enigmatic salivary gland tumor[J]. Head Neck Pathol, 2020, 14(4): 869-875. doi: 10.1007/s12105-020-01128-0
[31]	Haller F, Bieg M, Will R, et al. Enhancer hijacking activates oncogenic transcription factor NR4A3 in acinic cell carcinomas of the salivary glands[J]. Nat Commun, 2019, 10(1): 368. doi: 10.1038/s41467-018-08069-x pmid: 30664630
[32]	Haller F, Skálová A, Ihrler S, et al. Nuclear NR4A3 immunostaining is a specific and sensitive novel marker for acinic cell carcinoma of the salivary glands[J]. Am J Surg Pathol, 2019, 43(9):1264-1272. doi: 10.1097/PAS.0000000000001279 pmid: 31094928
[33]	Andreasen S, Varma S, Barasch N, et al. The HTN3-MSANTD3 fusion gene defines a subset of acinic cell carcinoma of the salivary gland[J]. Am J Surg Pathol, 2019, 43(4):489-496. doi: 10.1097/PAS.0000000000001200 pmid: 30520817
[34]	Urano M, Nakaguro M, Yamamoto Y, et al. Diagnostic significance of HRAS mutations in epithelial-myoepithelial carcinomas exhibiting a broad histopathologic spectrum[J]. Am J Surg Pathol, 2019, 43(7):984-994. doi: 10.1097/PAS.0000000000001258 pmid: 30994537
[35]	Bishop JA, Westra WH. MYB translocation status in salivary gland epithelial-myoepithelial carcinoma: Evaluation of classic, variant, and hybrid forms[J]. Am J Surg Pathol, 2018, 42(3): 319-325. doi: 10.1097/PAS.0000000000000990 pmid: 29135517
[36]	Agaimy A, Fonseca I, Martins C, et al. NUT carcinoma of the salivary glands: Clinicopathologic and molecular analysis of 3 cases and a survey of NUT expression in salivary gland carcinomas[J]. Am J Surg Pathol, 2018, 42(7): 877-884. doi: 10.1097/PAS.0000000000001046 pmid: 29649019
[37]	Rooper LM, Jo VY, Antonescu CR, et al. Adamantinoma-like Ewing sarcoma of the salivary glands: A newly recognized mimicker of basaloid salivary carcinomas[J]. Am J Surg Pathol, 2019, 43(2): 187-194. doi: 10.1097/PAS.0000000000001171 pmid: 30285997
[38]	Bishop JA, Alaggio R, Zhang L, et al. Adamantinoma-like Ewing family tumors of the head and neck: A pitfall in the differential diagnosis of basaloid and myoepithelial carcinomas[J]. Am J Surg Pathol, 2015, 39(9): 1267-1274. doi: 10.1097/PAS.0000000000000460 pmid: 26034869

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