TPM3‑NTRK1基因易位的乳头状甲状腺癌

M. R. Savchuk, N. Shved, N. Savelov, I. Plaksa
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Thus, all criteria of thyroid cancer with detected translocation in NTRK genes found in the literature were used. If the tumor met the criteria we performed an immunohistochemistry study with Ventana pan-TRK (EPR17341) Assay antibodies was performed on a BenchMark Ultra immunoassayer. In case of a positive immunohistochemistry reaction, next-generation sequencing on the Illumina HiSeq high-throughput genome-wide sequencing system.Results. Of the 130 cases analyzed, we identified 10 cases of tumor with histological features characteristic of NTRK positive thyroid cancer. In all cases, the disease was characterized by an indolent course, a slow increase in the tumor over a long time. In patient 5, a tumor of the thyroid gland was combined with extra-organ sarcoma of the retroperitoneal space. The sizes of the tumor node varied from 0.5 . 0.5 cm to 4.0 . 3.0 cm. All patients had metastases to the lymph nodes, in 3 cases the tumor grew beyond the thyroid capsule. 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摘要

该研究的目的是确定NTRK基因易位的乳头状甲状腺癌的特定形态学标准特征。材料和方法。回顾性分析了莫斯科卫生局莫斯科市肿瘤医院62号收治的130例经形态学证实的甲状腺乳头状癌病例。免疫组织化学研究的形态学选择标准是:淋巴结转移灶、微钙化、肿瘤甲状腺外扩散、囊状/瘤内结缔组织区存在、浸润(进入肿瘤囊、血管、淋巴管)、核内假包涵体存在、卵泡数量< 5%。因此,采用文献中发现的所有检测到NTRK基因易位的甲状腺癌标准。如果肿瘤符合标准,我们使用Ventana pan-TRK (EPR17341)进行免疫组织化学研究,在BenchMark Ultra免疫测定仪上进行检测抗体。如果免疫组化反应阳性,在Illumina HiSeq高通量全基因组测序系统上进行下一代测序。在分析的130例病例中,我们发现10例肿瘤具有NTRK阳性甲状腺癌的组织学特征。在所有病例中,这种疾病的特点是一个缓慢的过程,肿瘤在很长一段时间内缓慢增加。在患者5中,甲状腺肿瘤合并腹膜后间隙器官外肉瘤。肿瘤结的大小从0.5不等。0.5厘米至4.0。3.0厘米。所有患者均有淋巴结转移,其中3例肿瘤生长超出甲状腺包膜。根据NTRK抗体免疫组化研究结果(10名申请者中)1例检测到突变。在95%的肿瘤细胞中观察到不同程度的细胞质表达。TPM3‑NTRK1易位通过下一代测序得到证实。本研究展示了使用形态学标准检测NTRK基因突变甲状腺肿瘤的可能性。在更大样本的情况下,将有可能确定具有NTRK突变的肿瘤的结构特征。这将澄清形态学标准并增加检测突变的可能性,这在选择治疗方法(处方靶向治疗)时至关重要。
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Papillary thyroid cancer with translocation in the TPM3‑NTRK1 gene
The study objective – to identify specific morphological criteria characteristic of papillary thyroid cancer with translocations in the NTRK genes.Materials and methods. A retrospective analysis of 130 cases of morphologically confirmed papillary thyroid cancer from the archives of the Moscow City Oncology Hospital No 62, Moscow Healthсare Department was performed. The morphological selection criteria for the immunohistochemical study were: metastatic lesions of the lymph nodes, microcalcifications, extrathyroid spread of the tumor, the presence of a capsule / intratumorous areas of connective tissue, invasion (into the tumor capsule, blood vessels, lymphatic vessels), the presence of intranuclear pseudo-inclusions, the follicle quantity <5 %. Thus, all criteria of thyroid cancer with detected translocation in NTRK genes found in the literature were used. If the tumor met the criteria we performed an immunohistochemistry study with Ventana pan-TRK (EPR17341) Assay antibodies was performed on a BenchMark Ultra immunoassayer. In case of a positive immunohistochemistry reaction, next-generation sequencing on the Illumina HiSeq high-throughput genome-wide sequencing system.Results. Of the 130 cases analyzed, we identified 10 cases of tumor with histological features characteristic of NTRK positive thyroid cancer. In all cases, the disease was characterized by an indolent course, a slow increase in the tumor over a long time. In patient 5, a tumor of the thyroid gland was combined with extra-organ sarcoma of the retroperitoneal space. The sizes of the tumor node varied from 0.5 . 0.5 cm to 4.0 . 3.0 cm. All patients had metastases to the lymph nodes, in 3 cases the tumor grew beyond the thyroid capsule. According to the results of an immunohistochemical study with antibodies to NTRK (out of 10 applicants) mutation was detected in 1 case. Cytoplasmic expression of varying severity was observed in 95 % of tumor cells. TPM3‑NTRK1 translocation was confirmed by next-generation sequencing.Conclusion. The presented study demonstrates the possibility of using morphological criteria for detecting thyroid tumors with mutations in the NTRK genes. In the case of a larger sample, it will be possible to identify the structural features of tumors with NTRK mutations. This will clarify morphological criteria and increase the probability of detecting a mutation, which is essential when choosing treatment methods (prescribing targeted therapy).
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