ret/PTC-1, -2, and -3 oncogene rearrangements in human thyroid carcinomas: implications for metastatic potential?
ret/PTC-1, -2, and -3 oncogene rearrangements in human thyroid carcinomas: implications for metastatic potential?
复制标题
人类甲状腺癌中的 ret/PTC-1、-2 和 -3 癌基因重排：对转移潜力的影响？
DOI：
10.1210/jcem.81.9.8784097
复制
发表时间：
1996
期刊：
影响因子：
--
通讯作者：
S. Asa
中科院分区：
文献类型：
--
作者：
S. Sugg;Lei Zheng;I. Rosen;J. Freeman;S. Ezzat;S. Asa
ret/PTC 癌基因是甲状腺乳头状癌所特有的。该癌基因的三种形式由三个不同基因易位至 ret 原癌基因的酪氨酸激酶结构域而形成，导致组成型激酶激活。与临床结果的相关性存在争议； ret/PTC-1 被认为可以预测攻击行为。没有 ret/PTC 阳性肿瘤的形态学描述。我们分析了 60 例甲状腺癌的 ret/PTC 表达，以确定与临床病史、疾病阶段或肿瘤形态的相关性。从冷冻组织中提取的核糖核酸进行反转录；进行 PCR 扩增 ret/PTC-1、2 和 -3。 TPC-1细胞系是ret/PTC-1的阳性对照。所有肿瘤均具有形态学特征。收集临床数据。 44 名女性患者和 15 名男性患者切除了 57 例乳头状癌和 3 例滤泡状癌。诊断时的平均年龄为 46.2 岁（范围：24-83 岁）。 3名患者有颈部照射史。诊断时，11 例患者肿瘤扩散至甲状腺外，20 例有淋巴结转移，1 例有肺转移。 13 名患者患有高细胞乳头状癌； 3个肿瘤有局灶性岛叶或间变性去分化。平均随访时间为13.4个月，期间有4名患者疾病复发。没有发生死亡事件。 1 例乳头状癌 (1.7%) ret/PTC-1 阳性，无 ret/PTC-2 阳性，2 例 (3.4%) ret/PTC-3 阳性。虽然所有3例含有ret/PTC重排的肿瘤患者年龄均在45岁以下（范围26-44岁）且肿瘤较小（<1.2cm），但这3例患者中2例出现淋巴结转移，第3例出现淋巴侵犯。 ret/PTC 癌基因表达与放射史不相关。总之，在 60 例甲状腺癌中的 3 例 (5%) 中发现了 ret/PTC 癌基因重排，但在具有侵袭性形态特征的肿瘤中不存在这种重排。然而，我们发现患有小型甲状腺癌的年轻患者（< 45 岁）中存在 ret/PTC 重排，显示出淋巴受累的倾向，这表明在该亚组肿瘤的发展中可能发挥作用。
The ret/PTC oncogene is unique to papillary thyroid cancer. Three forms of this oncogene, formed by translocation of three different genes to the tyrosine kinase domain of the ret protooncogene, result in constitutive kinase activation. Correlation with clinical outcome is controversial; ret/PTC-1 has been suggested to predict aggressive behavior. There is no morphological description of ret/PTC-positive tumors. We analyzed 60 thyroid carcinomas for ret/PTC expression to determine correlation with clinical history, disease stage, or tumor morphology. Ribonucleic acid extracted from frozen tissue was reverse transcribed; PCR was performed to amplify ret/PTC-1, 2, and -3. The TPC-1 cell line was the positive control for ret/PTC-1. All tumors were characterized morphologically. Clinical data were collected. The 57 papillary and 3 follicular carcinomas were resected from 44 female patients and 15 males. The average age at diagnosis was 46.2 yr (range. 24-83 yr). Three patients had a history of neck irradiation. At diagnosis, 11 patients had extrathyroidal tumor extension, 20 had lymph node metastases, and 1 had lung metastasis. Thirteen patients had tall cell papillary carcinomas; 3 tumors had focal insular or anaplastic dedifferentiation. The average follow-up was 13.4 months, during which 4 patients had recurrent disease. No deaths occurred. One papillary carcinoma (1.7%) was positive for ret/PTC-1, none was positive for ret/PTC-2, and 2(3.4%) were positive for ret/PTC-3. Although all 3 patients who had tumors containing ret/PTC rearrangements were under the age of 45 yr (range, 26-44 yr) and had small tumors (< 1.2 cm), 2 of these 3 patients presented with lymph node metastases, and the third had lymphatic invasion. ret/PTC oncogene expression did not correlate with radiation history. In summary, ret/PTC oncogene rearrangements were found in 3 of 60 (5%) thyroid carcinomas and were not present in tumors with aggressive morphological features. However, we found ret/PTC rearrangements in young patients (< 45 yr of age) with small thyroid carcinomas showing a predisposition for lymphatic involvement, suggesting a possible role in the development of this subgroup of tumors.