唾液分泌型癌中出现非典型/不平衡 ETV6/NTRK3 重排：重点关注其发生率、模式及临床意义。

Atypical/unbalanced ETV6/NTRK3 rearrangement in salivary secretory carcinoma with a focus on the incidence, the patterns, and the clinical implications.

机构信息

Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China.

Department of Oral and Maxillo-facial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China.

出版信息

J Oral Pathol Med. 2022 Sep;51(8):721-729. doi: 10.1111/jop.13341. Epub 2022 Aug 17.

DOI:10.1111/jop.13341

PMID:36087274

Abstract

BACKGROUND

Atypical/unbalanced rearrangement in salivary secretory carcinoma was observed and its incidence, patterns, and clinical significance remain unknown.

METHODS

One hundred and ninety-six cases of diagnosed secretory carcinoma were retrospectively reviewed. Fluorescence in situ hybridization for NTRK3/ETV6::NTRK3 was conducted on cases carrying the atypical ETV6 fluorescence in situ hybridization signals. Cases without ETV6::NTRK3 were selected for next-generation sequencing to reveal novel partner. Immunohistochemistry and follow-up were performed.

RESULTS

Twenty-seven cases were confirmed to carry the atypical ETV6 fluorescence in situ hybridization signal patterns. The most common type of abnormality was the duplication of ETV6 5' end (1Y1GnR, n ≥ 2) with the incidence of 81.5% (22/27). Seventeen of 19 were identified with ETV6::NTRK3 and 2 with ETV6::RET. The immunophenotype was similar to the typical secretory carcinoma group. TrkC exhibited 68.8% sensitivity and 100% specificity for NTRK3 fusion. Microscopically, 5 out of 21 were accompanied by necrosis and 3 out of 21 showed neural invasion. Four out of 19 patients showed local relapse, 2 developed distant metastasis, and 1 died of disease. The patients with distant metastasis and even dead were both harbored ETV6::RET rearrangement. Statistical analysis revealed that there were no significant differences in disease-free survival, relapse-free survival, and distant metastasis-free survival between atypical and typical groups.

CONCLUSION

Gene rearrangement can be identified although the fluorescence in situ hybridization signals were atypical, which was instructive for secretory carcinoma diagnosis in clinical practice. The signals of partners were also always atypical which may have an impact to the efficacy of targeted drugs. There was no statistical evidence that this group possessed worse prognosis. However, secretory carcinomas with ETV6::RET have dismal prognosis than those with ETV6::NTRK3.

摘要

背景

唾液分泌型癌中观察到非典型/不平衡重排，其发生率、模式和临床意义尚不清楚。

方法

回顾性分析 196 例诊断为分泌型癌的病例。对携带非典型 ETV6 荧光原位杂交信号的病例进行 NTRK3/ETV6::NTRK3 荧光原位杂交。选择没有 ETV6::NTRK3 的病例进行下一代测序以揭示新的伙伴。进行免疫组织化学和随访。

结果

27 例被确认为携带非典型 ETV6 荧光原位杂交信号模式。最常见的异常类型是 ETV6 5'端的重复（1Y1GnR，n≥2），发生率为 81.5%（22/27）。19 例中有 17 例检测到 ETV6::NTRK3，2 例检测到 ETV6::RET。免疫表型与典型分泌型癌组相似。TrkC 对 NTRK3 融合的敏感性为 68.8%，特异性为 100%。显微镜下，21 例中有 5 例伴有坏死，21 例中有 3 例有神经侵犯。19 例患者中有 4 例出现局部复发，2 例发生远处转移，1 例死于疾病。发生远处转移甚至死亡的患者均存在 ETV6::RET 重排。统计分析显示，在无病生存、无复发生存和无远处转移生存方面，非典型组与典型组之间无显著差异。