结直肠高级别MANEC和NEC的临床病理特征及预后
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摘要
目的探讨结直肠高级别混合性腺神经内分泌癌(mixed adenoneuroendocrine carcinoma,MANEC)和神经内分泌癌(neuroendocrine carcinoma,NEC)的临床病理特征和预后。方法回顾性分析结直肠高级别MANEC(10例)及NEC(16例)的临床病理资料。采用免疫组织化学法检测神经内分泌标志物及转录因子。通过生存分析比较两组患者的生存率,对影响预后相关因素进行Cox回归分析。结果结直肠高级别MANEC和NEC患者发病部位差异具有统计学意义(P=0.014)。10例高级别MANEC中,7例发生淋巴结转移,其中71.4%的转移淋巴结内是神经内分泌癌成分,29.6%的转移淋巴结内是腺癌成分。16例NEC中,11例发生淋巴结转移,转移淋巴结内都是神经内分泌癌成分。高级别MANEC和NEC患者累积生存率比较差异无统计学意义(1年生存率80.0%vs75.0%,3年生存率17.1%vs 41.7%,P=0.275)。多因素分析结果显示,淋巴结转移是预后的独立影响因素(P=0.036)。结论结直肠高级别MANEC和NEC中的神经内分泌癌成分容易发生淋巴结转移,主导疾病进程。
Objective To investigate the clinicopathological features and prognosis of colorectal high-grade mixed adenoneuroendocrine carcinoma( MANEC) and neuroendocrine carcinoma( NEC). Methods The clinicopathological data of 10 cases of colorectal high-grade MANEC and 16 cases of NEC were retrospectively analyzed. The expression of neuroendocrine markers and transcription factors was detected by immunohistochemistry. The survival rates of the two groups were compared by the Kaplan-Meier survival analysis,and the prognostic factors were analyzed by Cox proportional regression model. Results The tumor location was significantly different between the two groups( P = 0. 014). In the 10 cases of high-grade MANEC,7 cases showed lymph node metastasis,among which 71. 4% of the metastatic cancer tissue were neuroendocrine carcinoma originated and 29. 6% were adenocarcinoma originated. In the 16 cases of NEC,lymph node metastasis was found in 11 cases,and all contained neuroendocrine carcinoma components. No significant cumulative survival difference was observed between the high-grade MANEC and the NEC group( 1-year survival rate: 80. 0% vs 75. 0%,3-year survival rate: 17. 1% vs 41. 7%,P = 0. 275). Lymph node metastasis was suggested to be an independent risk factor of disease prognosis by multivariable analysis( P = 0. 036). Conclusion The neuroendocrine carcinoma component of colorectal high-grade MANEC and NEC is prone to develop lymph node metastasis and has a major impact on the disease process.
Objective To investigate the clinicopathological features and prognosis of colorectal high-grade mixed adenoneuroendocrine carcinoma( MANEC) and neuroendocrine carcinoma( NEC). Methods The clinicopathological data of 10 cases of colorectal high-grade MANEC and 16 cases of NEC were retrospectively analyzed. The expression of neuroendocrine markers and transcription factors was detected by immunohistochemistry. The survival rates of the two groups were compared by the Kaplan-Meier survival analysis,and the prognostic factors were analyzed by Cox proportional regression model. Results The tumor location was significantly different between the two groups( P = 0. 014). In the 10 cases of high-grade MANEC,7 cases showed lymph node metastasis,among which 71. 4% of the metastatic cancer tissue were neuroendocrine carcinoma originated and 29. 6% were adenocarcinoma originated. In the 16 cases of NEC,lymph node metastasis was found in 11 cases,and all contained neuroendocrine carcinoma components. No significant cumulative survival difference was observed between the high-grade MANEC and the NEC group( 1-year survival rate: 80. 0% vs 75. 0%,3-year survival rate: 17. 1% vs 41. 7%,P = 0. 275). Lymph node metastasis was suggested to be an independent risk factor of disease prognosis by multivariable analysis( P = 0. 036). Conclusion The neuroendocrine carcinoma component of colorectal high-grade MANEC and NEC is prone to develop lymph node metastasis and has a major impact on the disease process.
引文
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[14]Li Y,Yau A,Schaeffer D,et al.Colorectal glandularneuroendocrine mixed tumor:pathologic spectrum and clinical implications[J].Am J Surg Pathol,2011,35(3):413-425.
[15]Gurzu S,Kadar Z,Bara T,et al.Mixed adenoneuroendocrine carcinoma of gastrointestinal tract:report of two cases[J].World J Gastroenterol,2015,21(4):1329-1333.
[16]Chen MH,Kuo YJ,Yeh YC,et al.High neuroendocrine component is a factor for poor prognosis in gastrointestinal high-grade malignant mixed adenoneuroendocrine neoplasms[J].J Chin Med Assoc,2015,78(8):454-459.
[17]Fukuba N,Yuki T,Ishihara S,et al.Gastric mixed adenoneuroendocrine carcinoma with a good prognosis[J].Intern Med,2014,53(22):2585-2588.
[18]Paniz Mondolfi AE,Slova D,Fan W,et al.Mixed adenoneuroendocrine carcinoma(MANEC)of the gallbladder:a possible stem cell tumor[J].Pathol Int,2011,61(10):608-614.
[19]Vanacker L,Smeets D,Hoorens A,et al.Mixed adenoneuroendocrine carcinoma of the colon:molecular Pathogenesis and treatment[J].Anticancer Res,2014,34(10):5517-5521.
[20]Scardoni M,Vittoria E,Volante M,et al.Mixed adenoneuroendocrine carcinomas of the gastrointestinal tract:targeted next-generation sequencing suggests a monoclonal origin of the two components[J].Neuroendocrinology,2014,100(4):310-316.
[21]余英豪,胡舜.胃肠胰神经内分泌肿瘤临床病理的十个重要问题[J].临床与实验病理学杂志,2015,31(10):1081-1084.
[22]郑树,张苏展,黄彦钦.结直肠癌研究30年回顾和现状[J].实用肿瘤杂志,2016,31(1):2-5.
[23]周海涛,周志祥.个性化个体化综合治疗是提高结直肠癌治愈率的最佳策略[J].实用肿瘤杂志,2014,29(3):202-204.
[2]La Rosa S,Marando A,Sessa F,et al.Mixed adenoueuroendcrine carcinomas(MANECs)of the gastrointestinal tract:an update[J].Cancers,2012,4(1):11-30.
[3]中国胃肠胰神经内分泌肿瘤病理专家组.中国胃肠胰神经内分泌肿瘤病理学诊断共识[J].中华病理学杂志,2011,40(4):257-262.
[4]Volante M,Rindi G,Papotti M.The grey zone between pure(neuro)endocrine and non-(neuro)endocrine tumours:a comment on concepts and classification of mixed exocrine-endocrine neoplasms[J].Virchows Arch,2006,449(5):499-506.
[5]张勇超,庄兢,韩广森,等.结直肠神经内分泌癌的临床诊治及预后[J].中华胃肠外科杂志,2011,14(12):955-957.
[6]邵玉铭,邢晓明,李宏,等.结直肠混合腺一神经内分泌癌病理特征和预后分析[J].齐鲁医学杂志,2013,28(3):216-218.
[7]Dalerba P,Sahoo D,Paik S,et al.CDX2 as a prognostic biomarker in stageⅡand stageⅢcolon cancer[J].N Engl J Med,2016,374(3):211-222.
[8]Zimmermann N,Lazar-Karsten P,Keck T,et al.Expression pattern of CDX2,estrogen and progesterone receptors in primary gastroenteropancreatic neuroendocrine tumors and metastases[J].Anticancer Res,2016,36(3):921-924.
[9]Marando A,Dainese E,La Rosa S,et al.Images in endocrine pathology:oncocytic dfferentiation in a mixed adenoneuroendocrine carcinoma of the colon[J].Endocr Pathol,2013,24(1):54-56.
[10]La Rosa S,Marando A,Furlan D,et al.Colorectal poorly differentiated neuroendocrine carcinomas and mixed adenoneuroendocrine carcinomas:insights into the diagnostic immunophenotype,assessment of methylation profile,and search for prognostic markers[J].Am J Surg Pathol,2012,36(4):601-611.
[11]Bari MF,Brown H,Nicholson AG,et al.BAI3,CDX2and VIL1:a panel of three antibodies to distinguish small cell from large cell neuroendocrine lung carcinomas[J].Histopathology,2014,64(4):547-556.
[12]Park JY,Ryu MH,Park YS,et al.Prognostic significance of neuroendocrine components in gastric carcinomas[J].Eur J Cancer,2014,50(16):2802-2809.
[13]Shia J,Tang LH,Weiser MR,et al.Is nonsmall cell type high-grade neuroendocrine carcinoma of the tubular gastrointestinal tract a distinct disease entity[J].Am J Surg Pathol,2008,32(5):719-731.
[14]Li Y,Yau A,Schaeffer D,et al.Colorectal glandularneuroendocrine mixed tumor:pathologic spectrum and clinical implications[J].Am J Surg Pathol,2011,35(3):413-425.
[15]Gurzu S,Kadar Z,Bara T,et al.Mixed adenoneuroendocrine carcinoma of gastrointestinal tract:report of two cases[J].World J Gastroenterol,2015,21(4):1329-1333.
[16]Chen MH,Kuo YJ,Yeh YC,et al.High neuroendocrine component is a factor for poor prognosis in gastrointestinal high-grade malignant mixed adenoneuroendocrine neoplasms[J].J Chin Med Assoc,2015,78(8):454-459.
[17]Fukuba N,Yuki T,Ishihara S,et al.Gastric mixed adenoneuroendocrine carcinoma with a good prognosis[J].Intern Med,2014,53(22):2585-2588.
[18]Paniz Mondolfi AE,Slova D,Fan W,et al.Mixed adenoneuroendocrine carcinoma(MANEC)of the gallbladder:a possible stem cell tumor[J].Pathol Int,2011,61(10):608-614.
[19]Vanacker L,Smeets D,Hoorens A,et al.Mixed adenoneuroendocrine carcinoma of the colon:molecular Pathogenesis and treatment[J].Anticancer Res,2014,34(10):5517-5521.
[20]Scardoni M,Vittoria E,Volante M,et al.Mixed adenoneuroendocrine carcinomas of the gastrointestinal tract:targeted next-generation sequencing suggests a monoclonal origin of the two components[J].Neuroendocrinology,2014,100(4):310-316.
[21]余英豪,胡舜.胃肠胰神经内分泌肿瘤临床病理的十个重要问题[J].临床与实验病理学杂志,2015,31(10):1081-1084.
[22]郑树,张苏展,黄彦钦.结直肠癌研究30年回顾和现状[J].实用肿瘤杂志,2016,31(1):2-5.
[23]周海涛,周志祥.个性化个体化综合治疗是提高结直肠癌治愈率的最佳策略[J].实用肿瘤杂志,2014,29(3):202-204.