Department of Pathology, University of Campinas/UNICAMP, Campinas, Brazil.
Department of Otolaryngology, IUOPA Hospital Universitario Central de Asturias, Oviedo, Spain.
Lab Invest. 2014 Jun;94(6):692-702. doi: 10.1038/labinvest.2014.59. Epub 2014 Apr 14.
Adenoid cystic carcinomas can occasionally undergo dedifferentiation, a phenomenon also referred to as high-grade transformation. However, cases of adenoid cystic carcinomas have been described showing transformation to adenocarcinomas that are not poorly differentiated, indicating that high-grade transformation may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form, which may encompass a wide spectrum of carcinomas in terms of aggressiveness. The aim of this study was to gain more insight in the biology of this pathological phenomenon by means of genetic profiling of both histological components. Using microarray comparative genomic hybridization, we compared the genome-wide DNA copy-number changes of the conventional and transformed area of eight adenoid cystic carcinomas with high-grade transformation, comprising four with transformation into moderately differentiated adenocarcinomas and four into poorly differentiated carcinomas. In general, the poorly differentiated carcinoma cases showed a higher total number of copy-number changes than the moderately differentiated adenocarcinoma cases, and this correlated with a worse clinical course. Special attention was given to chromosomal translocation and protein expression of MYB, recently being considered to be an early and major oncogenic event in adenoid cystic carcinomas. Our data showed that the process of high-grade transformation is not always accompanied by an accumulation of genetic alterations; both conventional and transformed components harbored unique genetic alterations, which indicate a parallel progression. Our data further demonstrated that the MYB/NFIB translocation is not necessarily an early event or fundamental for the progression to adenoid cystic carcinoma with high-grade transformation.
腺样囊性癌偶尔会发生去分化，这种现象也称为高级别转化。然而，已经描述了腺样囊性癌转化为非低分化腺癌的病例，这表明高级别转化不一定反映肿瘤进展的更晚期，而是向另一种组织学形式转化，这种转化可能包括在侵袭性方面具有广泛谱的癌。本研究旨在通过对两种组织学成分的遗传分析来更深入地了解这种病理现象的生物学特性。使用微阵列比较基因组杂交技术，我们比较了 8 例高级别转化的腺样囊性癌的常规和转化区域的全基因组 DNA 拷贝数变化，其中 4 例转化为中分化腺癌，4 例转化为低分化腺癌。一般来说，低分化腺癌病例的总拷贝数变化数高于中分化腺癌病例，并且这与更差的临床病程相关。特别关注了最近被认为是腺样囊性癌早期和主要致癌事件的 MYB 染色体易位和蛋白表达。我们的数据表明，高级别转化的过程并不总是伴随着遗传改变的积累；常规和转化成分都携带有独特的遗传改变，这表明是平行进展的。我们的数据进一步表明，MYB/NFIB 易位不一定是早期事件或向高级别转化的腺样囊性癌进展的基础。
