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韩国人群分化型甲状腺肿瘤中Gsα、ras、p53基因突变及ret/PTC重排的发生率

Prevalences of Gs alpha, ras, p53 mutations and ret/PTC rearrangement in differentiated thyroid tumours in a Korean population.

作者信息

Park K Y, Koh J M, Kim Y I, Park H J, Gong G, Hong S J, Ahn I M

机构信息

Department of Internal Medicine, Asan Institute for Life Sciences and Technology, Seoul, Korea.

出版信息

Clin Endocrinol (Oxf). 1998 Sep;49(3):317-23. doi: 10.1046/j.1365-2265.1998.00515.x.

Abstract

OBJECTIVE

In thyroid tumours, ras, Gs alpha, p53 mutations and ret/PTC rearrangement have been reported with variable prevalences in different geographical regions. We studied the prevalence of these mutations and rearrangement in thyroid tumours in a Korean population. As MDM2 and Bcl-1 protein expressions have been suggested to be associated with p53 protein, we also studied possible relationships among them.

PATIENTS AND DESIGN

Eleven cases of adenomatous goitre, eight cases of follicular adenoma, five cases of follicular carcinoma and 37 cases of papillary carcinoma were included in this study. To find mutations and rearrangement, RT-PCR, SSCP and/or direct sequencing, after subcloning if necessary, were used, and immunohistochemical stainings were performed for p53, MDM2 and Bcl-2 proteins in cases of papillary carcinoma.

RESULTS

We could not find any rearrangement for ret/PTC-1, -2, -3 and mutation of Gs alpha. For the ras oncogene, K and H-ras mutations were not found, but N-ras mutations, point mutation of CAA to CGA in codon 61, were detected in one follicular adenoma (12.5%, 1/8) and one follicular carcinoma (33%, 1/3). p53 mutations were detected in only one case of papillary carcinoma (3%, 1/31: exon 8, codon 266 GGA-->GAA). In 30 cases of papillary carcinoma without p53 mutation, the prevalences of positive immunohistochemical staining were 13.3% for p53 protein, 53.3% for MDM2 protein and 56.7% for Bcl-2 protein. While over-expression of p53 protein was not significantly related to that of MDM2 and Bcl-2 proteins, over-expression of MDM2 and Bcl-2 in papillary carcinoma were associated.

CONCLUSION

ret/PTC rearrangement, Gs alpha, ras and p53 mutations are relatively rare in differentiated thyroid neoplasms from a Korean population, which may reflect genetic and environmental differences from patients in countries with high prevalences. P53 protein over-expression was noted in 13.3% of papillary carcinoma cases without p53 mutation and was not significantly related to MDM2 and Bcl-2 expression.

摘要

目的

在甲状腺肿瘤中,已报道ras、Gsα、p53突变及ret/PTC重排在不同地理区域的发生率各不相同。我们研究了这些突变及重排在韩国人群甲状腺肿瘤中的发生率。由于已表明MDM2和Bcl-1蛋白表达与p53蛋白相关,我们也研究了它们之间可能的关系。

患者与设计

本研究纳入了11例腺瘤性甲状腺肿、8例滤泡性腺瘤、5例滤泡性癌及37例乳头状癌。为了发现突变及重排,必要时采用逆转录聚合酶链反应(RT-PCR)、单链构象多态性分析(SSCP)及/或直接测序,并对乳头状癌病例中的p53、MDM2及Bcl-2蛋白进行免疫组化染色。

结果

我们未发现ret/PTC-1、-2、-3的任何重排及Gsα的突变。对于ras癌基因,未发现K-ras和H-ras突变,但在1例滤泡性腺瘤(12.5%,1/8)和1例滤泡性癌(33%,1/3)中检测到N-ras突变,即密码子61处的CAA突变为CGA。仅在1例乳头状癌中检测到p53突变(3%,1/31:第8外显子,密码子266,GGA→GAA)。在30例无p53突变的乳头状癌中,p53蛋白免疫组化染色阳性率为13.3%,MDM2蛋白为53.3%,Bcl-2蛋白为56.7%。虽然p53蛋白的过表达与MDM2和Bcl-2蛋白的过表达无显著相关性,但乳头状癌中MDM2和Bcl-2的过表达相关。

结论

ret/PTC重排、Gsα、ras及p53突变在韩国人群的分化型甲状腺肿瘤中相对少见,这可能反映了与高发生率国家患者的遗传和环境差异。在13.3%无p53突变的乳头状癌病例中观察到p53蛋白过表达,且与MDM2和Bcl-2表达无显著相关性。

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