甲状腺乳头状癌中Cyclin D1、Ki-67表达和5项相关基因突变与远处转移的相关性研究

Relationship between distant metastasis and expression of cyclin D1 and Ki-67,and mutation of 5 related molecular markers in primary thyroid papillary cancer

目的:探讨Cyclin D1、Ki-67的表达和5项甲状腺癌相关基因突变与甲状腺乳头状癌(PTC)发生远处转移的关系。方法:收集2015年9月—2022年12月PTC发生远处转移病例(18例)和未发生转移病例(25例)的标本,采用免疫组化法检测Cyclin D1和Ki-67的蛋白表达,PCR法检测5项基因(KRAS、NRAS、BRAF、TERT和HRAS)突变情况,比较远处转移组和未转移组的组间差异。结果:①PTC远处转移组和未转移组中Cyclin D1的高表达率分别为72.2%和40.0%,Ki-67的高表达率分别为66.7%和36.0%,差异均具有统计学意义(P<0.05)。②在PTC远处转移组中检测到甲状腺癌相关5项基因改变15例次(其中BRAF V600E突变10例次,TERT启动子突变4例次,NRAS突变1例次);PTC未转移组中检测到基因改变15例次,均为BRAF V600E突变。③PTC远处转移组TERT突变率22.2%,显著高于PTC未转移组(0%),差异有统计学意义(P<0.05)。结论:Cyclin D1、Ki-67高表达或BRAF V600E和TERT启动子共突变可作为预测PTC发生远处转移的重要指标。

Objective:To explore the relationship between the expression of Cyclin D1 and Ki-67,as well as the mutation of five thyroid cancer related genes,and the occurrence of distant metastasis in papillary thyroid carcinoma(PTC).Methods:A total of 43 specimens of PTC cases with distant metastasis(n=18)and PTC cas-es without metastasis(n=25)from September 2015 to December 2022 were collected.The protein expression of Cyclin D1 and Ki-67 was detected using immunohistochemical methods,and mutation in 5 genes(KRAS,NRAS,BRAF,TERT,and HRAS)was detected using PCR method.The expression of Cyclin D1 and Ki-67 and the mutation of 5 genes between the two groups were compared.Results:OThe high expression rates of Cyclin D1 and Ki-67 in the PTC distant metastasis group and non-metastatic group were 72.2%and 40.0%,66.7%and 36.0%,respectively,with statistically significant differences(P<0.05).A total of 15 gene changes were detected in PTC distant metastasis group(including 10 BRAF V600E mutations,4 TERT promoter muta-tions,and 1 NRAS mutation),while among the non-metastatic PTC patients,15 gene changes were all BRAF V600E mutations.The TERT mutation rate in the PTC distant metastasis group was 22.2%,higher than that in the PTC non-metastatic group(0%),with a statistically significant difference(P<0.05).Conclusion:High expression of Cyclin DI and Ki-67,or co-mutation of BRAF V600E and TERT promoters can serve as important indicators for predicting distant metastasis of papillary thyroid cancer.