涎腺腺样囊性癌中MYB蛋白的表达及其意义
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摘要
目的探讨MYB在不同来源和不同级别涎腺腺样囊性癌(adenoid cystic carcinoma,ACC)中的表达及临床意义。方法收集内蒙古医科大学附属医院病理科存档的资料完整的涎腺肿瘤手术标本103例,其中64例涎腺ACC(组织学分级Ⅰ级19例、Ⅱ级27例、Ⅲ级18例)为实验组,选取同期7例涎腺外ACC和32例涎腺非ACC的良、恶性肿瘤作为对照组。采用免疫组化En Vision两步法检测两组中MYB蛋白表达。结果 MYB在64例涎腺ACC和7例涎腺外ACC中的阳性率分别为54. 69%(35/64)和57. 14%(4/7),差异无显著性(P> 0. 05)。MYB在64例涎腺ACC和32例涎腺非ACC良、恶性肿瘤中的阳性率分别为54. 69%(35/64)、6. 25%(2/32),差异有显著性(P <0. 05)。MYB在64例涎腺ACCⅠ、Ⅱ、Ⅲ级中的阳性率分别为68. 42%(13/19)、66. 67%(18/27)、14. 29%(4/18),差异有显著性(P <0. 05);其中Ⅰ级与Ⅱ级相比,差异无显著性(P>0. 016 7),Ⅰ、Ⅱ级与Ⅲ级相比差异有显著性(P <0. 016 7)。结论 MYB在涎腺ACCⅠ、Ⅱ级中高表达,在Ⅲ级中低表达,推测ACCⅢ级可能存在其它融合基因改变。MYB蛋白在涎腺非ACC良、恶性肿瘤中表达较低,提示MYB蛋白表达对于涎腺ACC的诊断具有诊断价值。
Purpose To investigate the role of MYB in adenoid cystic carcinoma( ACC) of different origins and grades.Methods A total of 103 specimens of salivary gland tumors with complete pathologic data were collected from the Department of Pathology,Affiliated Hospital of Inner Mongolia Medical University. 64 cases of ACC of the salivary gland,which included 19 cases of grade I,27 cases of grade Ⅱ,and 18 cases of grade Ⅲ were selected as experimental group. 7 cases of exrras-alivary ACC and 32 cases of non-ACC benign and malignant tumor of salivary gland were served as control group. The MYB protein expression was detected by MYB immunohistochemical En Vision two-step staining for both experimental and control group. Results The positive expression rates of MYB in 64 cases of salivary ACC and 7 cases of extrasalivary ACC were54. 69%( 35/64) and 57. 14%( 4/7),respectively,with no statistically significant difference( P > 0. 05). The positive expression rates of MYB in 64 cases of salivary ACC and 32 cases of non-ACC salivary benign and malignant tumors were54. 69%( 35/64) and 6. 25%( 2/32),respectively,which showed statistically significant difference( P < 0. 05). The positive expression rates of MYB were 68. 42%( 13/19),66. 67%( 18/27) and 14. 29%( 4/18) in 64 cases of salivary ACC Ⅰ,Ⅱ and Ⅲ,respectively,and the difference was significant( P <0. 05). The difference between grade Ⅰ and Ⅱ was not statistically significant( P > 0. 016 7),while compared with grade Ⅲ,there was a statistical increase of positive expression rate of MYB in both grade Ⅰ and Ⅱ( P < 0. 016 7). Conclusion MYB is highly expressed in grade I and Ⅱ of the salivary ACC and low expressed in grade Ⅲ. It is speculated that there may be other fusion gene mutation in salivary ACC grade Ⅲ. MYB is lowly expressed in non-ACC benign and malignant tumors of salivary gland,suggesting that MYB protein expression has a certain diagnostic value for the diagnosis of salivary ACC.
Purpose To investigate the role of MYB in adenoid cystic carcinoma( ACC) of different origins and grades.Methods A total of 103 specimens of salivary gland tumors with complete pathologic data were collected from the Department of Pathology,Affiliated Hospital of Inner Mongolia Medical University. 64 cases of ACC of the salivary gland,which included 19 cases of grade I,27 cases of grade Ⅱ,and 18 cases of grade Ⅲ were selected as experimental group. 7 cases of exrras-alivary ACC and 32 cases of non-ACC benign and malignant tumor of salivary gland were served as control group. The MYB protein expression was detected by MYB immunohistochemical En Vision two-step staining for both experimental and control group. Results The positive expression rates of MYB in 64 cases of salivary ACC and 7 cases of extrasalivary ACC were54. 69%( 35/64) and 57. 14%( 4/7),respectively,with no statistically significant difference( P > 0. 05). The positive expression rates of MYB in 64 cases of salivary ACC and 32 cases of non-ACC salivary benign and malignant tumors were54. 69%( 35/64) and 6. 25%( 2/32),respectively,which showed statistically significant difference( P < 0. 05). The positive expression rates of MYB were 68. 42%( 13/19),66. 67%( 18/27) and 14. 29%( 4/18) in 64 cases of salivary ACC Ⅰ,Ⅱ and Ⅲ,respectively,and the difference was significant( P <0. 05). The difference between grade Ⅰ and Ⅱ was not statistically significant( P > 0. 016 7),while compared with grade Ⅲ,there was a statistical increase of positive expression rate of MYB in both grade Ⅰ and Ⅱ( P < 0. 016 7). Conclusion MYB is highly expressed in grade I and Ⅱ of the salivary ACC and low expressed in grade Ⅲ. It is speculated that there may be other fusion gene mutation in salivary ACC grade Ⅲ. MYB is lowly expressed in non-ACC benign and malignant tumors of salivary gland,suggesting that MYB protein expression has a certain diagnostic value for the diagnosis of salivary ACC.
引文
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[8]Brayer K J,Frerich C A,Kang H,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.
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[10]Martelotto L G,De Filippo M R,Ng C K Y,et al.Genomic landscape of adenoid cystic carcinoma of the breast[J].J Pathol,2015,237(2):179-189.
[11]Drier Y,Cotton M J,Williamson K E,et al.An oncogenic MYBfeedback loop drives alternate cell fates in adenoid cystic carcinoma[J].Nat Genet,2016,48(3):265-272.
[12]Rettig E M,Talbot C,Sausen M,et al.Whole-genome sequencing of salivary gland adenoid cystic carcinoma[J].Cancer Prev Res,2016,9(4):265-274.
[13]Pusztaszeri M P,Sadow P M,Ushiku A,et al.MYB immunostaining is a useful ancillary test for distinguishing adenoid cystic carcinoma from pleomorphic adenoma in fine-needle aspiration biopsy specimens[J].Cancer Cytopathol,2014,122(4):257-265.
[14]刘尧,刘月平.WHO(2017)涎腺肿瘤分类解读[J].临床与实验病理学杂志,2018,34(1):1-3.
[15]Liu J,Shao C,Tan M L,et al.Molecular biology of adenoid cystic carcinoma[J].Head Neck,2012,34(11):1665-1677.
[16]Mitani Y,Liu B,Rao P,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.
[17]Fujii K,Murase T,Beppu S,et al.MYB,MYBL1,MYBL2,and NFIB gene alterations and MYC overexpression in salivary gland adenoid cystic carcinoma[J].Histopathology,2017,71(5):823-834.
[2]Brahmer J R,Tykodi S S,Chow L Q M,et al.Safety and activity of anti-PD-L1 antibody in patients with advanced cancer[J].NEngl J Med,2012,366(26):2455-2465.
[3]Ho A S,Kannan K,Roy D M,et al.The mutational landscape of adenoid cystic carcinoma[J].Nat Genet,2013,45(7):791-798.
[4]Bell D,Roberts D,Karpowicz M,et al.Clinical significance of Myb protein and downstream target genes in salivary adenoid cystic carcinoma[J].Cancer Biol Ther,2011,12(7):569-573.
[5]von Holstein S L,Fehr A,Persson M,et al.Adenoid cystic carcinoma of the lacrimal gland:MYB gene activation,genomic imbalances,and clinical characteristics[J].Ophthalmology,2013,120(10):2130-2138.
[6]D’Alfonso T M,Mosquera J M,Mac Donald T Y,et al.MYB-NFIB gene fusion in adenoid cystic carcinoma of the breast with special focus paid to the solid variant with basaloid features[J].Hum Pathol,2014,45(11):2270-2280.
[7]George O L,Ness S A.Situational awareness:regulation of the myb transcription factor in differentiation,the cell cycle and oncogenesis[J].Cancers,2014,6(4):2049-2071.
[8]Brayer K J,Frerich C A,Kang H,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.
[9]West R B,Kong C,Clarke N,et al.MYB expression and translocation in adenoid cystic carcinomas and other salivary gland tumors with clinicopathologic correlation[J].Am J Surg Pathol,2011,35(1):92-99.
[10]Martelotto L G,De Filippo M R,Ng C K Y,et al.Genomic landscape of adenoid cystic carcinoma of the breast[J].J Pathol,2015,237(2):179-189.
[11]Drier Y,Cotton M J,Williamson K E,et al.An oncogenic MYBfeedback loop drives alternate cell fates in adenoid cystic carcinoma[J].Nat Genet,2016,48(3):265-272.
[12]Rettig E M,Talbot C,Sausen M,et al.Whole-genome sequencing of salivary gland adenoid cystic carcinoma[J].Cancer Prev Res,2016,9(4):265-274.
[13]Pusztaszeri M P,Sadow P M,Ushiku A,et al.MYB immunostaining is a useful ancillary test for distinguishing adenoid cystic carcinoma from pleomorphic adenoma in fine-needle aspiration biopsy specimens[J].Cancer Cytopathol,2014,122(4):257-265.
[14]刘尧,刘月平.WHO(2017)涎腺肿瘤分类解读[J].临床与实验病理学杂志,2018,34(1):1-3.
[15]Liu J,Shao C,Tan M L,et al.Molecular biology of adenoid cystic carcinoma[J].Head Neck,2012,34(11):1665-1677.
[16]Mitani Y,Liu B,Rao P,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.
[17]Fujii K,Murase T,Beppu S,et al.MYB,MYBL1,MYBL2,and NFIB gene alterations and MYC overexpression in salivary gland adenoid cystic carcinoma[J].Histopathology,2017,71(5):823-834.