肠型胃腺癌组织CDX2表达与临床表现和病理特征的关系

Relationship between CDX2 expression in intestinal gastric adenocarcinoma tissue and clinical and pathological characteristics

目的分析肠型胃腺癌患者胃癌组织中尾侧型同源转录因子2(CDX2)免疫组织化学情况与临床表现和病理特征的关系。方法回顾性收集2022年1-12月联勤保障部队第909医院手术切除的肠型胃腺癌90例患者临床资料。根据CDX2免疫组织化学染色情况将所有患者分为CDX2阳性组和CDX2阴性组。比较两组患者间的临床表现和病理学资料特点、免疫和靶向治疗分子特征,分析CDX2表达与患者二代基因测序结果关系。结果根据胃癌组织中CDX2和细胞角蛋白7(CK7)免疫组化染色结果划分,CDX2阳性/CK7阳性共38例(42.22%),是最常见表达模式,其次为CDX2阴性/CK7阳性共30例(33.33%),CDX2阳性/CK7阴性16例(17.78%),CDX2阴性/CK7阴性6例(6.67%)。CDX2阳性组患者的肿瘤最大直径[(2.56±0.85)cm]小于CDX2阴性组[(3.41±0.93)cm],差异有统计学意义(P<0.001)。与CDX2阴性组相比,CDX2阳性者的组织学分级G2~G4患者比例(66.67%vs.88.89%)低,肿瘤分期T3~T4比例(25.93%vs.66.67%)低,淋巴管血管侵犯(18.52%vs.55.56%)、神经周围侵犯(14.81%vs.50.00%)及淋巴结转移比例(14.81%vs.61.11%)均低(P<0.05)。CDX2阴性患者的HER-2表达阳性比例(6.67%vs.50.00%)更低(P<0.05)。CDX2阳性患者基因改变多与受体酪氨酸激酶(TRK)基因相关,包括EGFR、ERBB2、ERBB3、DDR2和MET,而CDX2阴性患者似乎与肿瘤抑制基因的改变更密切相关,包括BRCA2、PETN、RB1、SMARCA4、TSC1和ATRX。结论肠型胃腺癌具有一定异质性,可根据CDX2的表达情况分为两种亚型。CDX2阳性和CDX2阴性患者间具有不同的病理和分子特征,并可能具有不同的预后,值得进一步研究。

Objective To analyze the relationship between immunohistochemical patterns of caudal type homeobex transcription factor 2(CDX2)in gastric cancer tissue of patients with intestinal adenocarcinoma and its clinical and pathological features.Methods Clinical data of 90 patients with intestinal gastric adenocarcinoma who underwent surgical resection in the 909th Hospital of PLA Joint Logistics Support Force from January 2022 to December 2022 were retrospectively collected.According to the immunohistochemical staining of CDX2,all patients were divided into CDX2 positive and CDX2 negative groups.The clinical manifestations,pathological data,molecular characteristics of immunological and targeted therapy,and the relationship between CDX2 expression and second-generation gene sequencing results were compared between the two groups.Results According to immunohistochemical staining of CDX2 and CK7 in gastric cancer tissue,CDX2 positive/CK7 positive in 38 cases(42.22%)was the most common expression pattern,followed by CDX2 negative/CK7 positive in 30 cases(33.33%),CDX2 positive/CK7 negative in 16 cases(17.78%),and CDX2 negative/CK7 negative in 6 cases(6.67%).The maximum diameter of the tumor in the CDX2 positive group(2.56±0.85)cm was smaller than that in the CDX2 negative group[(3.41±0.93)cm](P<0.001).Compared with the CDX2 negative group,the proportion of patients with DX2 positive histological grade G2-G4 was lower(25.93%vs.66.67%),the tumor stage T3-T4 was lower(25.93%vs.66.67%),the proportion of lymphatic vessel vascular invasion(25.93%vs.66.67%),perineural invasion(14.81%vs.50.00%)and lymph node metastasis was lower(14.81%vs.61.11%)(P<0.05).The positive proportion of HER-2 expression(6.67%)was lower in CDX2 negative patients(50.00%)(P<0.05).The gene changes in CDX2 positive patients are mostly related to tyrosine kinase receptor(TRK)genes,including EGFR,ERBB2,ERBB3,DDR2 and MET,while those in CDX2 negative patients seem to be more closely related to changes in Tumor suppressor gene,including BRCA2,PETN,RB1,SMARCA4,TSC1 and ATRX.Conclusions Intestinal gastric adenocarcinoma has certain heterogeneity and can be divided into two subtypes according to CDX2 expression.CDX2-positive and CDX2-negative patients have different pathological and molecular characteristics and may have different prognosis,which is worthy of further study.