Distinct molecular profiles for histological subtypes of epithelial ovarian adenocarcinomas. Homo sapiens

Background: It has been shown that based on gene expression profiles, subgroups within epithelial ovarian cancers (EOC) can be identified. We studied a well characterized series of ovarian carcinomas from patients treated at our institute using gene expression profiling to better define clinically significant subgroups. Methods: Gene expression profiling was performed using RNA of 90 primary fresh frozen EOC samples representing all histological subtypes and stages (FIGO I-IV). Patients underwent either primary or interval debulking surgery and if indicated taxane-based chemotherapy. Pathology was reviewed for all cased and complete follow-up, including treatment response and recurrences was available for all patients. Results: Unsupervised and supervised analysis of gene expression data showed distinct subtypes correlating with histology. Mucinous carcinoma was the most distinct subtype based on gene expression profile. No significant differences in gene expression profile between high and low grade serous carcinomas could be observed. No gene expression signatures associated with survival or treatment response could be identified. Conclusion: Histological subtypes of ovarian adenocarcinomas are characterized by distinct gene expression profiles. In order to find signatures correlated to outcome of treatment it is essential that gene expression profiling studies are performed in histological homogeneous groups. Overall design: 90 fresh frozen EOC samples representing all histological subtypes (53 high grade serous, 8 low grade serous, 14 undifferentiated, 6 mucinous, 6 enodometrioid en 3 clear cell carcinomas) and all FIGO stages (10 I-IIA and 80 IIB-IV)

背景：已有研究证实，基于基因表达谱可鉴定上皮性卵巢癌（EOC）内部的亚型。本研究针对本中心收治患者的一系列特征明确的卵巢癌样本开展基因表达谱分析，以期进一步明确具有临床意义的卵巢癌亚型。

方法：本研究对90例原发性新鲜冰冻上皮性卵巢癌样本进行基因表达谱分析，样本涵盖所有组织学亚型与FIGO分期（I-IV期）。所有患者均接受初始肿瘤细胞减灭术或间隔肿瘤细胞减灭术，必要时予以紫杉烷类化疗。所有病例均经过病理复核，且所有患者均获得完整随访数据，包括治疗反应与复发情况。

结果：对基因表达数据开展无监督与有监督分析后，发现存在与组织学类型相关的特征迥异的亚型。其中黏液性腺癌的基因表达谱特征最为独特。高级别与低级别浆液性癌之间未观察到显著的基因表达谱差异。未发现与患者生存或治疗反应相关的基因表达特征。

结论：卵巢腺癌的组织学亚型具有独特的基因表达特征。为挖掘与治疗结局相关的基因表达特征，需在组织学均一的组别中开展基因表达谱分析研究。

整体研究设计：本研究纳入90例新鲜冰冻上皮性卵巢癌样本，覆盖所有组织学亚型：高级别浆液性癌53例、低级别浆液性癌8例、未分化癌14例、黏液性腺癌6例、子宫内膜样癌6例及透明细胞癌3例；同时涵盖所有FIGO分期：I-IIA期10例、IIB-IV期80例。