野生型RET和RET/PTC融合基因在成人散发性甲状腺乳头状癌中的表达及其意义

目的探讨野生型BET（WT-RET）及RET／PTC1、3融合基因在成人散发性甲状腺乳头状癌（PTC）中的表达及其与临床病理学指标的关系和意义。方法用逆转录-聚合酶链反应（RT-PCR）检测102例石蜡与新鲜（43例）甲状腺病变组织（PTC66例,对照组各种良恶性肿瘤及良性病变共36例）中WT-RET和RET／PTC1、3融合基因的表达并结合临床资料进行分析。结果（1）62％（41／66）PTC患者≥40岁。38％（25／66）PTC伴淋巴细胞性甲状腺炎,59％（39／66）伴淋巴结转移,5例（7.6％）有远处转移。（2）RET原癌基因的酪氨酸激酶区（BET-TK）检出率为68．1％（45／66）。BET原癌基因断裂点（BP）与TK的同时检出率在PTC中28．8％（19／66）,腺瘤中12．5％（1／8）,表明存在WT-BET转录物。（3）RET／PTC检出率21．2％（14／66）,其中5例BET／PTC1阳性（7．6％）,9例RET／PTC3阳性（13．6％）。6例（9％）PTC同时表达BET／PTC和WT-BET。36例对照组病例中未检测到RET／PTC融合基因。（4）统计学分析,PTC病例中WT-BET与RET／PTC1融合基因的表达与性别、年龄、肿瘤大小、多灶性、伴淋巴细胞浸润及淋巴结转移等临床病理学指标无关（P〉0．05）。结论RET／PTC融合基因在散发性成人PTC中表达率低,其诊断和判断预后的价值不大。WT-BET在甲状腺肿瘤的滤泡形成过程中起一定作用。

Expressions of wildtype-RET and RET/PTC rearrangements in sporadic adult papillary thyroid carcinoma and their clinicopathologic correlation

Objective To evaluate the expressions of wildtype-RET (WT-RET) and RET/PTC in sporadic adult papillary thyroid carcinoma and to investigate their clinicopathologic correlation. Methods Sixty-six papillary thyroid carcinomas (PTC) and thirty-six control cases with frozen and paraffin-embedded tissues were analyzed for the expressions of WT-RET and oncogene RET/PTC1 or RET/PTC3 by nested RT-PCR. Results (1) 62 percent (41/66) of PTC patients were above 40 years of age. Thirty-eight percent(25/66) of the tumors showed lymphocytic thyroiditis. Lymph node and distant metastasis were seen in 59%(39/66)and 7.6%(5/66) respectively. (2) Forty-five cases (68.1%) of PTCs expressed RET tyrosine kinase domain (RET-TK). Simultaneous expressions of RET-BP and TK were seen in nineteen PTCs (28.8 %). One of eight adenomas (12.5 %) expressed wild-type RET (WT-RET). (3) Fourteen PTCs (21.2%) expressed RET/PTC, including five cases expressing RET/PTC1 and nine cases expressing RET/PTC3. Six cases(9%)expressed both RET/PTC and WT-RET. (4) Statistic analysis did not show any correlation between the expression of WT-RET or RET/PTC and clinicopathologic parameters. Conclusions The expression of RET/PTC was specific to PTC. However, its prevalence was low and, therefore, of limited diagnostic utility. The expression patterns of WT-RET in PTC and adenoma suggest that there are different molecular mechanisms in activating RET proto-oncogene in thyroid tumors.