Use of Mitotic Activity and the Size of Any Dedifferentiated Component for Risk Assessment in MDM2-Amplified Liposarcoma.

Hao Wu, Madina Sukhanova, Haiming Tang, Xinyan Lu, Minghao Zhong, Hari Deshpande, Seth M Pollack, William B Laskin, Borislav A Alexiev
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Abstract

Context.—: The characteristic molecular signature for both atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma is amplified sequences derived from chromosome 12q13-15, including MDM2 proto-oncogene (MDM2). As the progression of atypical lipomatous tumor/well-differentiated liposarcoma to the more aggressive dedifferentiated liposarcoma has the potential to adversely affect patient outcomes, the extent of the latter component might be important to evaluate.

Objective.—: To investigate the correlation between clinicopathologic characteristics, including tumor size, modified Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade, molecular data, and outcomes in 123 surgically resected MDM2-amplified liposarcomas.

Design.—: Pathology reports and clinical records were reviewed. A log-rank test was used to compare the survival trends, and univariate logistic regression was performed to identify variables associated with adverse events (distant metastasis and/or death), from which the P value was derived to construct a multivariate regression model.

Results.—: In univariate analysis, the largest single dimension of the dedifferentiated component, the percentage of cells with gain of chromosome 12, mitotic count, and the presence of modified FNCLLC grade 3 were associated with adverse events. In multivariate analysis, the largest single dimension of the dedifferentiated component (odds ratio: 1.169; 95% CI: 1.053, 1.299; P = .003), and a higher mitotic count (odds ratio: 1.133; 95% CI: 1.037, 1.237; P = .006) were correlated with adverse events. There was no statistically significant association between current local recurrence status, overall largest tumor dimension, overall tumor volume, MDM2 copy number, or MDM2 to chromosome 12 centromere probe ratio and adverse outcomes.

Conclusions.—: Staging dedifferentiated liposarcoma based on the size of the dedifferentiated component better predicts the outcome.

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利用有丝分裂活性和任何已分化成分的大小来评估 MDM2 扩增脂肪肉瘤的风险
背景非典型脂肪瘤/良好分化型脂肪肉瘤和低分化型脂肪肉瘤的特征性分子特征是来自染色体12q13-15的扩增序列,包括MDM2原癌基因(MDM2)。由于非典型脂肪瘤/分化良好的脂肪肉瘤向侵袭性更强的分化型脂肪肉瘤发展可能会对患者的预后产生不利影响,因此对后者的程度进行评估可能非常重要:研究123例手术切除的MDM2-扩增型脂肪肉瘤的临床病理特征(包括肿瘤大小、改良的法国国家癌症中心(FNCLCC)分级、分子数据)与预后之间的相关性:对病理报告和临床记录进行了审查。采用对数秩检验比较生存趋势,并进行单变量逻辑回归以确定与不良事件(远处转移和/或死亡)相关的变量,从中得出P值以构建多变量回归模型:在单变量分析中,去分化成分的最大单一维度、12号染色体增益细胞的百分比、有丝分裂计数和出现修正的FNCLLC 3级与不良事件相关。在多变量分析中,去分化成分的最大单维(几率比:1.169;95% CI:1.053,1.299;P = .003)和有丝分裂计数较高(几率比:1.133;95% CI:1.037,1.237;P = .006)与不良事件相关。目前的局部复发状况、肿瘤最大总尺寸、肿瘤总体积、MDM2拷贝数或MDM2与12号染色体中心粒探针比值与不良后果之间没有统计学意义:结论:根据已分化脂肪肉瘤的大小对其进行分期能更好地预测预后。
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