Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Genes Chromosomes Cancer. 2021 Jan;60(1):26-37. doi: 10.1002/gcc.22899. Epub 2020 Oct 28.
Dedifferentiated liposarcoma (DDLPS) is a relatively common soft tissue sarcoma that results from the progression of well-differentiated liposarcoma (WDLPS). This study aimed to investigate the progression process and to clarify the pathological and genetic factors related to poor prognosis in DDLPS. In 32 DDLPS cases and five WDLPS cases, genetic factors were analyzed by custom comparative genomic hybridization (CGH) array, which was designed to densely cover gene regions known to be frequently amplified in WD/DDLPS. The analyses comparing primary and metastatic lesions and those comparing histologically different areas in the same tumor revealed intra-tumoral genetic heterogeneity and progression. According to a prognostic analysis comparing the good-prognosis and the poor-prognosis groups, we selected MDM2 and HMGA2 as candidate genes associated with poor and good prognosis, respectively. The ratios of the amplification or gain levels of MDM2 and HMGA2 expressed in log ratios (log[MDM2/HMGA2] = log[MDM2]-log[HMGA2]) were significantly associated with prognosis. An amplification or gain level of MDM2 that was more than twice that of HMGA2 (MDM2/HMGA2 > 2, log[MDM2/HMGA2] > 1) was strongly related to poor OS (P < .001) and poor distant metastasis-free survival (DMFS) (P < .001). In the pathological analysis of 44 cases of DDLPS, histological tumor grade, cellular atypia, and MDM2 immunoreactivity were related to overall survival (OS), while HMGA2 immunoreactivity tended to be associated with OS. Cellular atypia was also associated with DMFS. In conclusion, histological grade and MDM2 expression were determined to be prognostically important, and the MDM2/HMGA2 amplification or gain ratio was found to have significant prognostic value by the custom CGH array analysis.
去分化脂肪肉瘤（DDLPS）是一种相对常见的软组织肉瘤，源自分化良好的脂肪肉瘤（WDLPS）的进展。本研究旨在探讨进展过程，并阐明与 DDLPS 预后不良相关的病理和遗传因素。在 32 例 DDLPS 病例和 5 例 WDLPS 病例中，通过定制的比较基因组杂交（CGH）阵列分析了遗传因素，该阵列设计用于密集覆盖已知在 WD/DDLPS 中频繁扩增的基因区域。比较原发和转移病变以及比较同一肿瘤中组织学不同区域的分析揭示了肿瘤内遗传异质性和进展。根据比较预后良好组和预后不良组的预后分析，我们选择了 MDM2 和 HMGA2 作为分别与不良和良好预后相关的候选基因。MDM2 和 HMGA2 的扩增或增益水平的表达的对数比（log[MDM2/HMGA2] = log[MDM2] - log[HMGA2]）与预后显著相关。MDM2 的扩增或增益水平超过 HMGA2 的两倍（MDM2/HMGA2 > 2，log[MDM2/HMGA2] > 1）与不良 OS（P <.001）和不良远处无复发生存（DMFS）（P <.001）密切相关。在 44 例 DDLPS 的病理分析中，组织学肿瘤分级、细胞异型性和 MDM2 免疫反应性与总生存（OS）相关，而 HMGA2 免疫反应性倾向于与 OS 相关。细胞异型性也与 DMFS 相关。总之，组织学分级和 MDM2 表达被确定为预后重要因素，通过定制的 CGH 阵列分析发现 MDM2/HMGA2 扩增或增益比具有显著的预后价值。
