Department of Gynaecological Oncology, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands.
Cell Oncol (Dordr). 2012 Jun;35(3):181-8. doi: 10.1007/s13402-012-0077-5. Epub 2012 May 12.
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.
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.
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.
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.
由于早期和晚期卵巢癌的临床表现明显不同,我们旨在阐明这些疾病实体是否仅通过诊断时间来区分,还是由不同的分子事件引起的。
纳入了 16 例早期和 16 例晚期卵巢癌,这些肿瘤在组织学亚型和分化程度上相匹配。通过 array comparative genomic hybridization 比较每个早期和晚期卵巢癌的基因组异常。为了研究这些异常与肿瘤的临床特征的相关性,我们根据基因组异常对肿瘤进行聚类。
晚期癌症的基因组畸变模式与早期癌症相同,但在晚期更为常见(p = 0.012)。基于基因组畸变的无监督聚类产生了两个显著区分早期和晚期的聚类(p = 0.001),并且在生存方面存在显著差异(p = 0.002)。然而,这些聚类比组织学亚型或分化程度能更准确地预测预后。
本研究表明,晚期卵巢癌要么从早期进展而来,要么从共同的前体病变发展而来,但它们不是由不同的致癌分子事件引起的。此外,我们表明 array comparative genomic hybridization 有潜力识别具有临床意义的不同患者。