Genetic Aberrations Relate Early and Advanced Stage Ovarian Cancer and are Associated with Survival. Homo sapiens

BACKGROUND: Because of the distinct clinical presentation of early and advanced stage ovarian cancer, we aim to clarify whether these disease entities are solely separated by time of diagnosis or whether they arise from distinct molecular events. METHODS: Sixteen early and sixteen advanced stage ovarian carcinomas, matched for histological subtype and differentiation grade, were included. Genomic aberrations were compared for each early and advanced stage ovarian cancer by array comparative genomic hybridization. To study how the aberrations correlate to the clinical characteristics of the tumors we clustered tumors based on the genomic aberrations. RESULTS: The genomic aberration patterns in advanced stage cancer equalled those in early stage, but were more frequent in advanced stage (p = 0.012). Unsupervised clustering based on genomic aberrations yielded two clusters that significantly discriminated early from advanced stage (p = 0.001), and that did differ significantly in survival (p = 0.002). These clusters however did give a more accurate prognosis than histological subtype or differentiation grade. CONCLUSION: This study indicates that advanced stage ovarian cancer either progresses from early stage or from a common precursor lesion but that they do not arise from distinct carcinogenic molecular events. Furthermore, we show that array comparative genomic hybridization has the potential to identify clinically distinct patients. Overall design: Sixteen early and sixteen advanced stage ovarian carcinomas

背景：鉴于早期与晚期卵巢癌具有截然不同的临床表现，本研究旨在明确这两类疾病是否仅以诊断时间相区分，抑或是起源于不同的分子事件。
方法：本研究纳入16例早期卵巢癌与16例晚期卵巢癌，两组在组织学亚型与分化等级上进行匹配。通过阵列比较基因组杂交（array comparative genomic hybridization）检测基因组畸变，并对早期与晚期卵巢癌分别开展基因组畸变对比分析。为探究基因组畸变与肿瘤临床特征的关联，本研究基于基因组畸变对肿瘤进行聚类。
结果：晚期卵巢癌的基因组畸变模式与早期卵巢癌一致，但晚期病例的畸变发生率更高（p = 0.012）。基于基因组畸变的无监督聚类得到两个聚类群，二者可显著区分早期与晚期卵巢癌（p = 0.001），且患者的生存情况存在显著差异（p = 0.002）。相较于组织学亚型或分化等级，该聚类群可提供更为精准的预后评估。
结论：本研究表明，晚期卵巢癌要么由早期卵巢癌进展而来，要么起源于共同的前驱病变，而非源于不同的致癌分子事件。此外，本研究证实阵列比较基因组杂交具备识别临床特征不同的患者的潜力。
整体实验设计：纳入16例早期卵巢癌与16例晚期卵巢癌。