Institute of Pathology, Charité University Hospital Berlin, Berlin, Germany.
Tumorbank Ovarian Cancer Network, Berlin, Germany.
Histopathology. 2018 Dec;73(6):1002-1012. doi: 10.1111/his.13711. Epub 2018 Oct 7.
Advanced-stage ovarian high-grade serous carcinoma (HGSC) is a poor-prognosis cancer; however, a small and poorly characterised subset of patients shows long-term survival. We aimed to establish a cohort of HGSC long-term survivors for histopathological and molecular analysis.
Paraffin blocks from 151 patients with primary FIGO III/IV HGSC and progression-free survival (PFS) >5 years were collected within the Tumorbank Ovarian Cancer (TOC) Network; 77 HGSC with a PFS <3 years were used as a control group. A standardised analysis of histological type and morphological features was performed. Ki67 index, tumour-infiltrating lymphocytes (TILs) and major histocompatibility complex expression (MHC1/2) were determined by immunohistochemistry. A total of 117 of 151 tumours (77.5%) in the long-term survivor group fulfilled the World Health Organisation (WHO) criteria of HGSC after review, and of these, 83 patients (70.9%) fulfilled all clinical criteria for inclusion into our cohort. Tumours of long-term survivors had significantly higher CD3 and CD8 TILs and were more frequently positive for MHC2 than controls (P = 0.004, P = 0.025, P = 0.048). However, there were also long-term survivors (up to 20%) with low TILs or low MHC expression. TILs and MHC had no impact on survival in long-term survivors. Morphological and Ki67 analysis revealed no differences between long-term survivors and controls.
HGSC from long-term survivors have higher-level T cell infiltration and antigen-presentation capacity; however, this is not a prerequisite for an excellent prognosis. Histopathological criteria are not capable to identify these patients. Further extensive clinical and molecular characterisation of this enigmatic subgroup is ongoing to understand the reasons of long-term survival in HGSC.
晚期卵巢高级别浆液性癌(HGSC)预后较差,但有一小部分特征不明显的患者表现出长期生存。我们旨在建立一个 HGSC 长期幸存者队列,进行组织病理学和分子分析。
在肿瘤库卵巢癌(TOC)网络中收集了 151 名原发性FIGO III/IV 期 HGSC 且无进展生存期(PFS)>5 年的患者的石蜡块;将 77 名 PFS<3 年的 HGSC 患者作为对照组。对组织学类型和形态特征进行了标准化分析。采用免疫组织化学法测定 Ki67 指数、肿瘤浸润淋巴细胞(TILs)和主要组织相容性复合体表达(MHC1/2)。在长期幸存者组的 151 例肿瘤中,有 117 例(77.5%)经审查符合世界卫生组织(WHO)HGSC 标准,其中 83 例(70.9%)符合纳入本队列的所有临床标准。长期幸存者的肿瘤 CD3 和 CD8 TILs 明显更高,MHC2 阳性率也明显高于对照组(P=0.004,P=0.025,P=0.048)。然而,也有长期幸存者(高达 20%)的 TILs 或 MHC 表达水平较低。TILs 和 MHC 对长期幸存者的生存没有影响。TILs 和 MHC 对长期幸存者和对照组之间的生存没有影响。形态学和 Ki67 分析显示长期幸存者和对照组之间没有差异。
来自长期幸存者的 HGSC 具有更高水平的 T 细胞浸润和抗原呈递能力;然而,这不是良好预后的必要条件。组织病理学标准无法识别这些患者。正在对这一神秘亚组进行更广泛的临床和分子特征描述,以了解 HGSC 长期生存的原因。