Department of Pathology and Laboratory Medicine, Sinai Health System, Toronto, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Mod Pathol. 2019 Jun;32(6):884-892. doi: 10.1038/s41379-018-0198-0. Epub 2019 Feb 1.
The special AT-rich sequence binding protein 2 (SATB2) is a sensitive and specific diagnostic marker for colorectal adenocarcinoma and reduced expression of SATB2 is associated with a poor prognosis. Colitis-associated colorectal adenocarcinoma often shows distinct morphologic and molecular phenotypes compared to sporadic cases. However, the SATB2 expression profile in colitis-associated carcinoma has not been defined. We performed immunohistochemistry for SATB2 as well as CDX2, MUC5AC, MUC6 and mismatch repair proteins on 60 consecutive colitis-associated carcinomas from 58 inflammatory bowel disease patients and compared the expression profile to a control group of 32 sporadic colorectal carcinomas. Only 26 (43%) colitis-associated carcinomas expressed SATB2, compared to 29 (91%) sporadic colorectal carcinomas (p < 0.0001). MUC5AC expression was more frequently observed in colitis-associated carcinomas than sporadic colorectal caracinomas (52% and 25% respectively; p = 0.013). Eight (13%) cases of colitis-associated carcinoma showed loss of CDX2 expression, which was retained in all of the sporadic controls (p = 0.047). In colitis-associated carcinoma, 50% of SATB2 negative cases had lymph node metastasis compared to only 15% of SATB2 positive cases (p = 0.007). Loss of SATB2 was particularly frequent in mucinous-type tumors, occurring in 83% of these cases. There was no significant association between SATB2 expression and mismatch repair protein status. These data show that the immunoprofile of colitis-associated carcinoma is different than that seen in sporadic cases. In particular, SATB2 is significantly less sensitive in colitis-associated carcinoma and it should be interpreted cautiously as a marker of colorectal origin in colitis patients. The association between loss of SATB2 and lymph node metastasis suggests that it may have similar prognostic value in the setting of inflammatory bowel disease as in sporadic cases.
富含特殊 AT 序列结合蛋白 2（SATB2）是结直肠腺癌的敏感且特异的诊断标志物，SATB2 的低表达与预后不良相关。与散发性病例相比，结肠炎相关性结直肠腺癌通常表现出明显的形态学和分子表型。然而，结肠炎相关性癌中的 SATB2 表达谱尚未确定。我们对 58 例炎症性肠病患者的 60 例连续结肠炎相关性癌进行了 SATB2 免疫组化以及 CDX2、MUC5AC、MUC6 和错配修复蛋白检测，并将表达谱与 32 例散发性结直肠癌的对照组进行了比较。只有 26 例（43%）结肠炎相关性癌表达 SATB2，而 29 例（91%）散发性结直肠癌表达 SATB2（p<0.0001）。结肠炎相关性癌中 MUC5AC 的表达频率高于散发性结直肠癌（分别为 52%和 25%；p=0.013）。8 例（13%）结肠炎相关性癌出现 CDX2 表达缺失，而所有散发性对照组均保留 CDX2 表达（p=0.047）。在结肠炎相关性癌中，SATB2 阴性病例中有 50%发生淋巴结转移，而 SATB2 阳性病例中仅有 15%发生淋巴结转移（p=0.007）。SATB2 缺失在黏液型肿瘤中尤为常见，占这些病例的 83%。SATB2 表达与错配修复蛋白状态之间没有显著关联。这些数据表明，结肠炎相关性癌的免疫表型与散发性病例不同。特别是 SATB2 在结肠炎相关性癌中的敏感性显著降低，因此在结肠炎患者中，SATB2 作为结直肠来源的标志物应谨慎解读。SATB2 缺失与淋巴结转移之间的关联表明，它在炎症性肠病中的预后价值可能与散发性病例相似。
