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唾液腺肿瘤的分子特征:作为诊断和预后标志物的潜在用途。

Molecular signature of salivary gland tumors: potential use as diagnostic and prognostic marker.

作者信息

Fonseca Felipe Paiva, Sena Filho Marcondes, Altemani Albina, Speight Paul M, Vargas Pablo Agustin

机构信息

Department of Oral Diagnosis (Pathology), Piracicaba Dental School, University of Campinas, Piracicaba, Brazil.

Department of Pathology, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil.

出版信息

J Oral Pathol Med. 2016 Feb;45(2):101-10. doi: 10.1111/jop.12329. Epub 2015 May 20.

Abstract

Salivary gland tumors are a highly heterogeneous group of lesions with diverse microscopic appearances and variable clinical behavior. The use of clinical and histological parameters to predict patient prognosis and survival rates has been of limited utility, and the search for new biomarkers that could not only aid in a better understanding of their pathogenesis but also be reliable auxiliaries for prognostic determination and useful diagnostic tools has been performed in the last decades with very exciting results. Hence, gene rearrangements such as CRTC1-MAML2 in mucoepidermoid carcinomas have shown excellent specificity, and more than that, it has been strongly correlated with low-grade tumors and consequently with an increased survival rate and better prognosis of patients affected by neoplasms carrying this translocation. Moreover, MYB-NFIB and EWSR1-ATF1 gene fusions were shown to be specifically found in cases of adenoid cystic carcinomas and hyalinizing clear cell carcinomas, respectively, in the context of salivary gland tumors, becoming reliable diagnostic tools for these entities and potential therapeutic targets for future therapeutic protocols. Finally, the identification of ETV6-NTRK3 in cases previously diagnosed as uncommon acinic cell carcinomas, cystadenocarcinomas, and adenocarcinomas not otherwise specified led to the characterization of a completely new and now widely accepted entity, including, therefore, mammary analogue secretory carcinoma in the list of well-recognized salivary gland carcinomas. Thus, further molecular investigations of salivary gland tumors are warranted, and the recognition of other genetic abnormalities can lead to the acknowledgment of new entities and the acquirement of reliable biomarkers.

摘要

涎腺肿瘤是一组高度异质性的病变,具有多样的微观表现和可变的临床行为。使用临床和组织学参数来预测患者的预后和生存率效用有限,在过去几十年里,人们一直在寻找新的生物标志物,这些标志物不仅有助于更好地理解其发病机制,而且能成为可靠的预后判定辅助指标和有用的诊断工具,并且取得了非常令人兴奋的成果。因此,黏液表皮样癌中的CRTC1-MAML2等基因重排显示出极佳的特异性,不仅如此,它还与低级别肿瘤密切相关,进而与携带这种易位的肿瘤患者的生存率提高和预后改善相关。此外,在涎腺肿瘤的背景下,MYB-NFIB和EWSR1-ATF1基因融合分别在腺样囊性癌和透明细胞透明变性癌中被特异性发现,成为这些实体的可靠诊断工具和未来治疗方案的潜在治疗靶点。最后,在先前诊断为不常见的腺泡细胞癌、囊腺癌和未另行指定的腺癌病例中鉴定出ETV6-NTRK3,导致了一个全新的、现已被广泛接受的实体的特征描述,因此,乳腺样分泌癌也被列入了公认的涎腺癌名单中。因此,有必要对涎腺肿瘤进行进一步的分子研究,识别其他基因异常可能会带来新实体的确认和可靠生物标志物的获得。

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