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

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

目的探讨野生型RET(WTRET)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(RTPCR)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WTRET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(RETTK)检出率为68.1%(45/66)。RET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WTRET转录物。(3)RET/PTC检出率21.2%(14/66),其中5例RET/PTC1阳性(7.6%),9例RET/PTC3阳性(13.6%)。6例(9%)PTC同时表达RET/PTC和WTRET。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WTRET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。WTRET在甲状腺肿瘤的滤泡形成过程中起一定作用。

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.