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Ret/PTC激活不影响成人甲状腺乳头状癌的临床和病理特征。

Ret/PTC activation does not influence clinical and pathological features of adult papillary thyroid carcinomas.

作者信息

Puxeddu Efisio, Moretti Sonia, Giannico Angela, Martinelli Marco, Marino Cecilia, Avenia Nicola, Cristofani Roberto, Farabi Raffaele, Reboldi Gianpaolo, Ribacchi Rodolfo, Pontecorvi Alfredo, Santeusanio Fausto

机构信息

Department of Internal Medicine, Division of Internal Medicine and Endocrine and Metabolic Science, University of Perugia, via E. del Pozzo, 06126 Perugia, Italy.

出版信息

Eur J Endocrinol. 2003 May;148(5):505-13. doi: 10.1530/eje.0.1480505.

Abstract

OBJECTIVE

RET proto-oncogene rearrangements (ret/PTCs) represent the most common genetic alterations found in papillary thyroid carcinomas (PTCs). Correlation of ret/PTC expression with clinical outcome is controversial. The aim of the present study was to analyze the frequency of RET rearrangements in adult PTCs, and to investigate if ret/PTCs influence biological behavior and clinical features of the cancers.

DESIGN

Ret/PTC rearrangements were looked for in tIssue samples of 48 PTCs collected at our institution. Data about clinical and pathological features of the tumors were also reviewed. Three separate association analyses were carried out on the cohort evaluating the effects of, respectively, ret/PTC positivity, preferential RET tyrosine kinase domain (RET-TK) expression, and ret/PTC plus RET-TK positivity, on age, sex, tumor size, staging, number of neoplastic foci, and histological subtype.

METHODS

The genetic study was conducted with the RT-PCR-Southern blot technique. Standard Student's t-test and Fisher exact test were applied for the association analyses.

RESULTS

The molecular genetic study demonstrated the positivity of ret/PTC1 and ret/PTC3 in 13 of 48 tumors (27.1%), and an exclusive or preferential RET-TK expression in 17 cases (35.4%). None of the three genetico-clinical analyses showed any significant association between ret/PTC expression and the clinical and pathological features of the cancers.

CONCLUSIONS

These data indicate that RET rearrangements may not play any distinctive role in driving histotype development and cancer progression in these neoplasms. Moreover, they weaken the possibility of using ret/PTC as a prognostic marker for papillary thyroid carcinomas.

摘要

目的

RET原癌基因重排(ret/PTCs)是甲状腺乳头状癌(PTCs)中最常见的基因改变。ret/PTC表达与临床结局的相关性存在争议。本研究的目的是分析成人PTCs中RET重排的频率,并研究ret/PTCs是否影响癌症的生物学行为和临床特征。

设计

在我们机构收集的48例PTCs组织样本中寻找ret/PTC重排。还回顾了肿瘤的临床和病理特征数据。对该队列进行了三项独立的关联分析,分别评估ret/PTC阳性、优先RET酪氨酸激酶结构域(RET-TK)表达以及ret/PTC加RET-TK阳性对年龄、性别、肿瘤大小、分期、肿瘤灶数量和组织学亚型的影响。

方法

采用RT-PCR- Southern印迹技术进行基因研究。采用标准的学生t检验和Fisher精确检验进行关联分析。

结果

分子遗传学研究显示,48例肿瘤中有13例(27.1%)ret/PTC1和ret/PTC3呈阳性,17例(35.4%)有排他性或优先性RET-TK表达。三项基因临床分析均未显示ret/PTC表达与癌症的临床和病理特征之间存在任何显著关联。

结论

这些数据表明,RET重排在这些肿瘤的组织类型发展和癌症进展中可能不发挥任何独特作用。此外,它们削弱了将ret/PTC用作甲状腺乳头状癌预后标志物的可能性。

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