Brachyury在脊索瘤诊断中的应用
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摘要
目的探讨Brachyury在脊索瘤中表达的敏感性和特异性,评价其应用价值。方法采用EnVision法检测Brachyury蛋白在40例骶骨脊索瘤中表达,另外选取40例组织形态与脊索瘤相类似的病例其中包括5例混合瘤(副脊索瘤/肌上皮瘤),8例骨外黏液样软骨肉瘤,10例肾透明细胞癌和17例富含黏液的软骨肉瘤作为对照。同时比较CK,vimentin、EMA和S-100在上述肿瘤中表达情况。结果 40例脊索瘤病例中,Brachyury全部表达(40/40),表达强度为轻-重度,退分化脊索瘤中退分化成分不表达,对照组40例病例中2例混合瘤(副脊索瘤/肌上皮瘤)、2例骨外黏液样软骨肉瘤和2例富含黏液的软骨肉瘤表达Brachyury(6/40),表达强度为轻-中度,经统计学分析,Brachury在本组实验中表达敏感性为100%,特异性为85%。结论 Brachury是诊断脊索瘤敏感性和特异性均较好的免疫标记物,可以作为一线抗体使用,但也需要结合组织形态特点,标本处理情况及其他免疫组化抗体CK、EMA、vimentin、S-100等综合判断。
Objective To investigate the diagnostic utility of Brachyury with its specifity and sensitivity in chordoma. Methods The immunohistochemical expression of Brachyury protein was retrospectively stained by EnVision system in 40 cases of chordoma and other 5 mixed tumours(parachordoma/myoepithelioma) of the bone, 8 extraskeletal myxoid chondrosarcoma, 10 clear cell carcinoma of kidney, and 17 chondrosarcoma with abundant myxoid stroma. CKpan, Vim, EMA and S-100 were all reviewed as well. Results 40 chordomas were positive for Brachyury with mild to strong staining except the dedifferentiated component in chordoma. In the control group, 2 cases of mixed tumor(parachordoma/myoepithelioma), 2 cases of extraskeletal mxyoid chondrosarcoma and 2 cases of chondrosarcoma with abundant myxoid stroma were also positive for Brachyury with mild to moderate staining. Sensitvity and specifity of Brachyury were 100% and 85%, respectively, in this study. Conclusion Brachyury is a highly specific and sensitive immunohistochmical marker for chordoma. Combination of histology, sampling process as well as other immunohistochemical markers including CKpan, Vim, EMA and S-100 is critical for diagnosis of chordoma.
Objective To investigate the diagnostic utility of Brachyury with its specifity and sensitivity in chordoma. Methods The immunohistochemical expression of Brachyury protein was retrospectively stained by EnVision system in 40 cases of chordoma and other 5 mixed tumours(parachordoma/myoepithelioma) of the bone, 8 extraskeletal myxoid chondrosarcoma, 10 clear cell carcinoma of kidney, and 17 chondrosarcoma with abundant myxoid stroma. CKpan, Vim, EMA and S-100 were all reviewed as well. Results 40 chordomas were positive for Brachyury with mild to strong staining except the dedifferentiated component in chordoma. In the control group, 2 cases of mixed tumor(parachordoma/myoepithelioma), 2 cases of extraskeletal mxyoid chondrosarcoma and 2 cases of chondrosarcoma with abundant myxoid stroma were also positive for Brachyury with mild to moderate staining. Sensitvity and specifity of Brachyury were 100% and 85%, respectively, in this study. Conclusion Brachyury is a highly specific and sensitive immunohistochmical marker for chordoma. Combination of histology, sampling process as well as other immunohistochemical markers including CKpan, Vim, EMA and S-100 is critical for diagnosis of chordoma.
引文
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[14] Sangoi AR,Karamchandani J,Lane B,et al.Specificity of brachury in the distinction of chordoma from clear cell renal cell carcinoma and germ cell tumors:a study of 305 cases[J].Mod Pathol,2011,24(3):425-429.
[15] Kaith Almefty,BBA,Svetlana Pravdenkova,Benedicto Colli,et al.Chordoma and Chondrosarcoma Similar,but Quite Different,skull Base Tumors[J].CANCER December 1,2007,110(11):2457-2465.
[16] Xiaohong R.Yang,David Ng,David A Alcorta,et al,T (Brachyury) gene duplication confers major susceptibility to familial chordoma[J].Nat Genet,2009,41(11):1176-1178.
[17] 杨珊珊,周晓军.脊索瘤的临床病理研究进展[J].临床与实验病理学杂志,2012,28(5):553-555.
[18] Markku Miettinen,Zengfeng Wang,Jerzy Lasota,et al,Nuclear brachyury expression is consistent in chordoma,common in germ cell tumors and small cell carcinomas and rare in other carcinomas and sarcomas.An immunohistochemical study of 5229 cases[J].Am J Surg Pathol,2015,39(10):1305-1312.
[19] S.Stacchiotti,A.Gronchi,P.Fossati,et al.Best practices for the management of local-regional recurrent chordoma:a position paper by the Chordoma Global Consensus Group[J].Ann Oncol,2017,28(6):1230-1242.
[2] Mukherjee D,Chaichana K L,Gokaslan Z L,et al.Survival of patients with malignant primary osseous spinal neoplasms:results from the surveillance,epidemiology,and end results (SEER) database from 1973 to 2003[J].J Neurosury Spine,2015,12(3):4298-4304.
[3] Christopher D.M.Fletcher,Julia A.Bridge,Pancras C.W.Hogendorn,WHO Classification of tumors of Soft Tissue and Bone,2013,IARC,Lyon.325-329.
[4] Ke Wang,Kaibing Tian,Junting Zhang,et al,Brachyury:A sensitive marker,but not a prognostic factor,for skull base chordomas[J].Molecular Medicine Reports,2015,12,4298-4304.
[5] Romeo S,Hogendoorn P C,Brachyury and chordoma:the chondroid-chordoid dilemma resolved[J].J Pathol,2006,209(2):143-146.
[6] R.Chugh,H.Tawbi.D.R.Lucas,J.S.Biermann,et al.Chordoma:the nonsarcoma primary bone tumor[J].Oncologist,2007,11,1344-1350.
[7] Yakkioui Y,van Overbeeke JJ,Santegoeds R,et al,Chordoma:the entity[J].Biochim Biophys Acta,2014,1846(2):655-669.
[8] Kreshak J,Larousserie F,Picci P,et al.Difficulty distinguishing benign notochordal cell tumor from chordoma further suggests a link between them[J].Cancer Imaging,2014,14:4.
[9] Yutaka Nibu,Diana S.Jose-Edwards,et al.From Notochord Formation to Hereditary Chordoma:The Many Roles of Brachyury[J].BioMed Research International,2013 Volume,1-8.
[10] Vujovic S,Henderson S,Presneau N,et al,Brachyury,a crucial regulator of notochordal development,is a novel biomarker for chordomas[J].J Patholo,2006,209(2):157-165.
[11] 倪建法,周光新,施鑫,等.脊索瘤的基础与临床研究进展[J].医学研究生学报,2015,28(2):203-206.
[12] Xin Sun,Francis Hornicek,Joseph H.Schwab,et al.Chordoma:an update on the pathophysiology and molecular mechanisms[J].Curr Rev Musculoskelet Med,2015,8:344-352.
[13] Oakley GJ,Fuhrer K,Seethala RR.Brachyury,SOX-9,and podoplanin,new markers in the skull base chordoma vs chondrosarcoma differential:a tissue microarray-based comparative analysis[J].Mod Pathol,2008,21(12):1461-1469.
[14] Sangoi AR,Karamchandani J,Lane B,et al.Specificity of brachury in the distinction of chordoma from clear cell renal cell carcinoma and germ cell tumors:a study of 305 cases[J].Mod Pathol,2011,24(3):425-429.
[15] Kaith Almefty,BBA,Svetlana Pravdenkova,Benedicto Colli,et al.Chordoma and Chondrosarcoma Similar,but Quite Different,skull Base Tumors[J].CANCER December 1,2007,110(11):2457-2465.
[16] Xiaohong R.Yang,David Ng,David A Alcorta,et al,T (Brachyury) gene duplication confers major susceptibility to familial chordoma[J].Nat Genet,2009,41(11):1176-1178.
[17] 杨珊珊,周晓军.脊索瘤的临床病理研究进展[J].临床与实验病理学杂志,2012,28(5):553-555.
[18] Markku Miettinen,Zengfeng Wang,Jerzy Lasota,et al,Nuclear brachyury expression is consistent in chordoma,common in germ cell tumors and small cell carcinomas and rare in other carcinomas and sarcomas.An immunohistochemical study of 5229 cases[J].Am J Surg Pathol,2015,39(10):1305-1312.
[19] S.Stacchiotti,A.Gronchi,P.Fossati,et al.Best practices for the management of local-regional recurrent chordoma:a position paper by the Chordoma Global Consensus Group[J].Ann Oncol,2017,28(6):1230-1242.