Institut CochinINSERM U1016, CNRS UMR8104, Paris Descartes University, Paris, France.
Medical Oncology Reference Center for Rare Adrenal DiseasesDepartment of Endocrinology, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France.
Eur J Endocrinol. 2018 May;178(5):R215-R230. doi: 10.1530/EJE-18-0027. Epub 2018 Feb 23.
Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis, the five-years overall survival being below 40%. However, there is great variability of outcomes and we have now a better view of the heterogeneity of tumor aggressiveness. The extent of the disease at the time of diagnosis, best assayed by the European Network for the Study of Adrenal Tumors (ENSAT) Staging Score, is a major determinant of survival. The tumor grade, including the mitotic count and the Ki67 proliferation index, also appears as a strong prognostic factor. The assessment of tumor grade, even by expert pathologists, still suffers from inter-observer reproducibility. The emergence of genomics in the last decade has revolutionized the knowledge of molecular biology and genetics of cancers. In ACC, genomic approaches - including pan-genomic studies of gene expression (transcriptome), recurrent mutations (exome or whole-genome sequencing), chromosome alterations, DNA methylation (methylome), miRNA expression (miRnome) - converge in a new classification of ACC, characterized by distinct molecular profiles and very different outcomes. Targeted measurements of a few discriminant molecular alterations have been developed in the perspective of clinical routine, and thus, may help defining therapeutic strategy. By individualizing patients' prognosis and tumor biology, these recent progresses appear as an important step forward towards precision medicine.
肾上腺皮质癌 (ACC) 是一种罕见的恶性肿瘤，预后不良，五年总生存率低于 40%。然而，其结局存在很大的变异性，我们现在对肿瘤侵袭性的异质性有了更好的了解。诊断时疾病的范围，最好通过欧洲肾上腺肿瘤研究网络 (ENSAT) 分期评分来评估，是生存的主要决定因素。肿瘤分级，包括有丝分裂计数和 Ki67 增殖指数，也表现为一个强有力的预后因素。即使由专家病理学家进行肿瘤分级评估，仍存在观察者间的可重复性问题。在过去十年中，基因组学的出现彻底改变了癌症的分子生物学和遗传学知识。在 ACC 中，基因组方法——包括基因表达（转录组）的泛基因组研究、反复出现的突变（外显子组或全基因组测序）、染色体改变、DNA 甲基化（甲基组）、miRNA 表达（miRnome）——汇聚成一种新的 ACC 分类，其特征是具有明显不同的分子特征和非常不同的结局。在临床常规的背景下，已经开发出针对少数有鉴别力的分子改变的靶向测量方法，因此，可能有助于确定治疗策略。通过对患者的预后和肿瘤生物学进行个体化评估，这些最新进展似乎是迈向精准医学的重要一步。
