CAJ | 학술논문

目的：探讨甲状腺乳头状癌( papillary thyroid carcinoma, PTC)中Cyclin D1表达上调和BRAF( V600E)突变的相关性及临床意义,分析二者在PTC发生、发展中的作用。方法采用免疫组化EnVision两步法检测52例PTC和52例甲状腺良性病变(结节性甲状腺肿25例、桥本甲状腺炎15例、滤泡性腺瘤12例)中Cyclin D1的表达；采用PCR法及DNA测序法检测上述标本中BRAF(V600E)突变状况,分析Cyclin D1表达上调和BRAF(V600E)突变的相关性及与PTC临床病理特征的关系。结果52例PTC中Cyclin D1阳性率为84．6%,免疫反应评分(4．6±2．4)与甲状腺良性病变(1．3±1．6)比较差异有统计学意义(t=8．525,P<0．01)；Cyclin D1表达上调与肿瘤淋巴结转移、包膜侵犯、肿瘤分期(Ⅲ+Ⅳ期)及BRAF(V600E)突变相关(P<0．05),与患者年龄、性别、肿瘤结节数目及直径无关。52例PTC中BRAF(V600E)突变率63．5%,甲状腺良性病变中突变率为0,差异有统计学意义(P<0．01),BRAF(V600E)突变与肿瘤淋巴结转移、包膜侵犯及肿瘤分期(Ⅲ+Ⅳ期)密切相关(P<0．05),与患者年龄、性别、肿瘤结节数目及直径无关。 BRAF(V600E)突变组中Cyclin D1表达强度更强,阳性率显著高于野生组(突变组100%,野生组57．9%),免疫表达评分均值高于野生组[突变组(5．7±1．6),野生组(4．0±2．5)],两组比较差异有统计学意义(t=2．652,P<0．05)。结论 Cyclin D1表达上调与BRAF(V600E)突变呈正相关,二者与PTC的发生、发展密切相关,可作为评估PTC侵袭转移能力的指标。
목적：탐토갑상선유두상암( papillary thyroid carcinoma, PTC)중Cyclin D1표체상조화BRAF( V600E)돌변적상관성급림상의의,분석이자재PTC발생、발전중적작용。방법채용면역조화EnVision량보법검측52례PTC화52례갑상선량성병변(결절성갑상선종25례、교본갑상선염15례、려포성선류12례)중Cyclin D1적표체；채용PCR법급DNA측서법검측상술표본중BRAF(V600E)돌변상황,분석Cyclin D1표체상조화BRAF(V600E)돌변적상관성급여PTC림상병리특정적관계。결과52례PTC중Cyclin D1양성솔위84．6%,면역반응평분(4．6±2．4)여갑상선량성병변(1．3±1．6)비교차이유통계학의의(t=8．525,P<0．01)；Cyclin D1표체상조여종류림파결전이、포막침범、종류분기(Ⅲ+Ⅳ기)급BRAF(V600E)돌변상관(P<0．05),여환자년령、성별、종류결절수목급직경무관。52례PTC중BRAF(V600E)돌변솔63．5%,갑상선량성병변중돌변솔위0,차이유통계학의의(P<0．01),BRAF(V600E)돌변여종류림파결전이、포막침범급종류분기(Ⅲ+Ⅳ기)밀절상관(P<0．05),여환자년령、성별、종류결절수목급직경무관。 BRAF(V600E)돌변조중Cyclin D1표체강도경강,양성솔현저고우야생조(돌변조100%,야생조57．9%),면역표체평분균치고우야생조[돌변조(5．7±1．6),야생조(4．0±2．5)],량조비교차이유통계학의의(t=2．652,P<0．05)。결론 Cyclin D1표체상조여BRAF(V600E)돌변정정상관,이자여PTC적발생、발전밀절상관,가작위평고PTC침습전이능력적지표。
Purpose To investigate the correlation of the expression of Cyclin D1 and BRAF ( V600E) mutation in papillary thyroid carcinoma ( PTC) and their clinical significance, and to analyze their role in the pathogenesis of PTC. Methods The expression of CK34βE12 and MC protein was detected by immunohistochemical EnVision method in 52 cases of PTC and 52 cases of thyroid benign lesions (25 cases of nodular goiters, 15 cases of Hashimoto’s thyroiditis, 12 cases of follicular adenoma), and the mutation status of BRAF gene protein in above specimens were detected by polymerase chain reaction and DNA sequencing. Expression of Cyclin D1 and BRAF (V600E) mutation in papillary thyroid carcinoma and their correlation clinicopathologic features were also analyzed. Results The positive rate of Cyclin D1 in 88 cases of PTC was 84. 6%,and the immunoreactivity score (4. 6 ± 2. 4), compared with thyroid be-nign lesions (1. 3 ± 1. 6), was statistically significant difference (t=8. 525, P<0. 01). Expression of Cyclin D1 was closely related with lymph node metastasis, capsular invasion, tumor stage Ⅲ+Ⅳ and BRAF (V600E) mutation (P<0. 05), but not related with age, gender, number and diameter of tumor nodules. In 52 cases of PTC BRAF gene mutation rate was 63. 5%, but in thyroid benign lesions mutation rate was 0, with significant difference (P<0. 01). The BRAF mutation is closely related with lymph node metastasis, capsular invasion and tumor stage Ⅲ+Ⅳ(P<0. 05), but not related with age, gender, number and diameter of tumor nodules. The expression of Cyclin D1 in BRAF (V600E) mutation group was stronger, the positive expression rate was significantly higher than that of wild group (100% vs 57. 9%), and expression of the mean score was higher than that of the wild group (5. 7 ± 1. 6 vs 4. 0 ± 2. 5);the comparison between the two groups showed statistical difference (t=2. 652, P<0. 05). Conclusions The expression of Cyclin D1 and BRAF (V600E) mutation are positively related, which are also closely related with the occurrence and development of PTC, and can be used as an index to predict the invasion and metastasis in PTC.