Lennerz Jochen K, van der Sloot Kimberley W J, Le Long Phi, Batten Julie M, Han Jae Young, Fan Kenneth C, Siegel Corey A, Srivastava Amitabh, Park Do Youn, Chen Jey-Hsin, Sands Bruce E, Korzenik Joshua R, Odze Robert D, Dias-Santagata Dora, Borger Darrell R, Khalili Hamed, Iafrate A John, Lauwers Gregory Y
Department of Pathology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, 02116, USA.
Division of Gastroenterology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
Int J Colorectal Dis. 2016 May;31(5):973-982. doi: 10.1007/s00384-016-2574-x. Epub 2016 Mar 30.
It is now recognized that Crohn's disease (CD), similar to ulcerative colitis (UC), carries an up to 20-fold higher cancer risk, and the development of colorectal carcinoma (CRC) is a major long-term complication. Once CRC is present, molecular profiling is one of the components in selecting appropriate treatment strategies; however, in contrast to UC, genetic alterations in Crohn's colitis-associated CRC are poorly understood.
In a series of 227 patients with Crohn's colitis, we identified 33 cases of CRC (~14 %) and performed targeted mutational analysis of BRAF/KRAS/NRAS and determined microsatellite status as well as immunophenotype of the tumors.
In the CRC cohort, the median age at time of cancer diagnosis was 58 (range 34-77 vs. 59.5 in sporadic; P = 0.81) and the median CD duration was 29 years (range 6-45). As a group, CRC complicating Crohn's colitis is BRAF (97 %) and NRAS (100 %) wild type and the vast majority is microsatellite stable (94 %); KRAS-mutations were found in six cases (18 %). Stage grouping, anatomic distribution, and overall survival were similar to sporadic CRC; however, long-standing CD (≥25 years) as well as gastric-immunophenotype (MUC5AC+) was associated with significantly shorter overall survival (P = 0.0029; P = 0.036, respectively).
In summary, the clinicopathological and molecular profile of CD-associated CRC is similar to that observed in sporadic CRC.
目前已认识到,克罗恩病(CD)与溃疡性结肠炎(UC)类似,患癌风险高达20倍,结直肠癌(CRC)的发生是一种主要的长期并发症。一旦出现CRC,分子谱分析是选择合适治疗策略的组成部分之一;然而,与UC不同,对克罗恩病相关性CRC的基因改变了解甚少。
在一系列227例克罗恩病患者中,我们鉴定出33例CRC(约14%),并对BRAF/KRAS/NRAS进行靶向突变分析,确定肿瘤的微卫星状态以及免疫表型。
在CRC队列中,癌症诊断时的中位年龄为58岁(范围34 - 77岁,散发性CRC为59.5岁;P = 0.81),CD的中位病程为29年(范围6 - 45年)。总体而言,并发于克罗恩病的CRC为BRAF(97%)和NRAS(100%)野生型,绝大多数为微卫星稳定(94%);6例(18%)发现KRAS突变。分期分组、解剖分布和总生存率与散发性CRC相似;然而,长期CD(≥25年)以及胃免疫表型(MUC5AC+)与总生存率显著缩短相关(分别为P = 0.0029;P = 0.036)。
总之,CD相关性CRC的临床病理和分子特征与散发性CRC相似。