甲状腺髓样癌中FOXA1表达及临床意义

Expression and clinical significance of FOXA1 inmedullary thyroid carcinoma

目的 探讨甲状腺髓样癌(MTC)组织中叉头盒A1(FOXA1)的表达,及其与临床病理特征和预后的关系。方法 收集2012年2月至2021年7月23例MTC手术患者标本。采用免疫组化染色和实时荧光定量PCR法(q PCR)检测MTC组织中FOXA1蛋白和mRNA表达。分析FOXA1表达与MTC临床病理特征以及预后的关系。结果 FOXA1蛋白表达主要定位于细胞质,19例(82.61%)阳性,其中5例(26.32%)降钙素受体(CTR)蛋白表达阴性。仅1例(4.35%) FOXA1蛋白和CTR蛋白表达均为阴性。FOXA1蛋白表达与年龄、性别、促结缔组织性增生、淀粉样沉积、肿瘤侵袭、甲状腺外延伸、RET基因状态无关(P>0.05);与肿瘤直径、TNM分期、Ras基因、PTEN蛋白表达有关(P<0.05)。MTC组织中FOXA1蛋白表达与术前血清CEA(r_(s)=0.291,P=0.704)、CT(r_(s)=0.373,P=0.805)水平均无关。MTC组织中FOXA1 mRNA相对表达量与FOXA1蛋白表达呈正相关(r_(s)=0.843,P<0.001)。4例FOXA1蛋白阴性表达患者全部获得生化治愈。8例死亡患者FOXA1蛋白免疫组化评分为5.0(4.0,10.0),明显高于其他15例存活患者[3.0(2.0,6.0)],差异具有统计学意义(P=0.019)。结论 FOXA1在MTC中呈阳性表达,且FOXA1蛋白高表达与疾病侵袭性进展及不良预后有关。

Objective To investigate the expression of forkhead box A1(FOXA1)in medullary thyroid carcinoma(MTC)and its relationship with clinicopathological features and prognosis.Methods From February 2012 to July 2021,the specimens of 23 MTC patients were collected.Immunohistochemical staining and real-time PCR(qPCR)were used to detect the expression of FOXA1 protein and mRNA in MTC tissues.The relationship between FOXA1 expression and clinicopathological features and prognosis of MTC was analyzed.Results The expression of FOXA1 protein was mainly localized in cytoplasm,19 cases(82.61%)were positive,and 5 cases(26.32%)were negative for calcitonin receptor(CTR)protein.Only one sample(4.35%)was negative for both FOXA1 protein and CTR protein.FOXA1 protein expression was not correlated with age,sex,desmoplastic hyperplasia,amyloid deposition,tumor invasion,extrathyroid extension and RET gene status(P>0.05).It was correlated with tumor diameter,TNM stage,Ras gene and PTEN protein expression(P<0.05).The expression of FOXA1 protein in MTC tissues was not correlated with preoperative serum CEA(r_(s)=0.291,P=0.704)and CT(r_(s)=0.373,P=0.805)levels.The relative expression of FOXA1 mRNA was positively correlated with FOXA1 protein expression in MTC tissues(r_(s)=0.843,P<0.001).All the 4 patients with negative expression of FOXA1 protein obtained biochemical cure.The immunohistochemical score of FOXA1 protein in 8 dead patients was 5.0(4.0,10.0),which was significantly higher than that in the other 15 surviving patients[3.0(2.0,6.0)],with significant differences(P=0.019).Conclusion FOXA1 expression is positive in MTC,and high expression of FOXA1 protein is associated with aggressive progression and poor prognosis of the disease.