肝内胆管细胞癌患者IDH1基因状态与组织学特征的关系

Relationship between IDH1 gene status and histological characteristics in patients with intrahepatic cholangiocarcinoma

目的探究肝内胆管细胞癌(ICC)患者异柠檬酸脱氢酶1(IDH1)基因状态与组织学特征之间的关系。方法选择经MSK-IMPACT靶向测序切除的ICC,并获取其临床数据。通过对IDH1基因状态盲法读取和幻灯片回顾的方式,收集其组织学特征、黏液分泌、坏死、纤维化、细胞质结构形态(低立方形、饱满立方形/多边形或柱状)及结构标本(吻合、管状、密集管状和团块状)。如果未占肿瘤≥75%的显性模式,则考虑结构异质性。结果比较203例ICC患者的mIDH1组(58例,28.6%)和wtIDH1组(145例,71.4%)参数,发现所有IDH1突变体肿瘤均为小管型组织学特征,且mIDH1病例更可能呈现饱满立方形/多边形(P<0.001)和纤维化(P<0.001)形态,而wtIDH1更可能呈低立方形(P<0.001),两组均为显著的结构异质性,但结构标本分布差异无统计学意义(P>0.05)。相比wtIDH1,mIDH1中常见饱满立方形/多边形细胞形态和肿瘤内纤维化,然而,IDH1突变与明显的组织形态无相关性。结论ICC患者的mIDH1基因状态和组织学特征有助于临床识别和IDH靶向治疗的发展。

Objective To describe the relationship between isocitrate dehydrogenase 1(IDH1)gene status and histological characteristics in patients with intrahepatic cholangiocarcinoma(ICC).Methods Resected ICCs with targeted next generation sequencing by MSK-IMPACT were selected.Clinical data were obtained.By slide review,blinded to IDH status,data were collected for histology type,mucin production,necrosis,fibrosis,cytoplasm cell shape(low cuboidal,plump cuboidal/polygonal,and columnar),and architectural pattern(anastomosing,tubular,compact tubular,and solid).A tumor was considered architecturally heterogeneous if no dominant pattern represented≥75%of the tumor.Results Compared with the parameters of mIDH1(58,28.6%)and wtIDH1(145,71.4%)groups in 203 patients with ICC,found that all IDH1 mutant tumors were of small duct type histology and mIDH1 cases were more likely to have plump cuboidal/polygonal shape(P<0.001)and geographic-type fibrosis(P<0.001)while IDH1 wild type were more likely to have low cuboidal shape(P<0.001).Both groups were predominantly architecturally heterogeneous with no significant difference in the distribution of architectural patterns(P>0.05).Plump cuboidal/polygonal cell shape and a geographic-type pattern of intra-tumoral fibrosis were more often seen in mIDH1 compared with IDH wild type tumors,however,IDH1 mutation was not associated with a distinct histoarchitectural pattern.Conclusion The IDH1 gene status and histological characteristics in patients with ICC can contribute to the development of clinical identification and IDH-targeted therapy.