结直肠癌中SATB2失表达与DNA错配修复蛋白缺失和BRAF突变相关

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  摘要:据报道,富含AT序列特异性结合蛋白(special AT-rich sequence binding protein 2, SATB2)被认为是结直肠癌一种特异性免疫组化标记物;然而,关于SATB2表达与结直肠癌中常见分子改变的关系尚不清楚。我们通过免疫组织化学方法检测了SATB2 在586例消化(gastrointestinal, GI)道和胰腺腺癌中的表达情况以评估其在诊断中的作用,并分析不同SATB2表达的结直肠癌的临床病理和分子特征。我们检测了266例下下GI道来源(246例结直肠癌和20例阑尾黏液腺癌)的腺癌、208例上下GI道和小肠来源(74例起源于食管/食管胃交界处、103例起源于胃、20例起源于十二指肠和11例起源于空回肠)的腺癌及112例胰腺导管腺癌中SATB2和CDX2的表达。与上下GI道、小肠或胰腺来源的腺癌(26/320, 8%)相比,SATB2表达更多见于下下GI道来源的腺癌(222/266, 83%)(P< 0.001)。与CDX2单阳性相比,下下GI道来源的腺癌更特异性呈现SATB2和CDX2的双阳性表达(SATB2+/CDX2+)(94% vs. 57%, P<0.001 )与SATB2阳性表达的结直肠腺癌相比,SATB2阴性表达的结直肠腺癌病例更容易出现MMR蛋白表达缺失(13/39, 33% VS.29/201, 14%, P<0.01)与SATB2表达阳性的肿瘤相比,SATB2表达缺失的肿瘤更容易检出 BRAFV600E 突变(29%vs.3%) (P<0.001)。总之,SATB2表达是下GI道起源肿瘤的相对特异性标志物;然而,SATB2表达的缺失更常见于MMR蛋白缺失和BRAF突変的结直肠癌。
  关键词:结直肠癌,SATB2, CDX2, DNA错配修复,BRAF,KRAS
(Am J Surg Pathol 2018;42:1409-1417)
美国外科病理学杂志中文版2019年第2期全文No.2
(蒋 慧 翻译 郑建明 审校)









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