Alves-Vale Catarina, Galvão Beatriz, Silvestre Ana Rita, Pereira José Silva, Bei Li, Fernandes João Paulo, Borralho Paula, Carmo-Fonseca Maria, Custódio Noélia
Department of Pathology, CUF Oncologia, Lisboa, Portugal.
Gulbenkian Institute for Molecular Medicine, Edifício Egas Moniz Avenida Professor Egas Moniz, Lisboa, 1649-028, Portugal.
J Ovarian Res. 2025 Aug 20;18(1):191. doi: 10.1186/s13048-025-01766-4.
Tubo-ovarian carcinoma, a leading cause of gynaecological-related mortality, holds substantial biological and clinical heterogeneity. Despite advancements in drug development, predicting therapeutic efficacy remains challenging, partly due to the limited availability of in vitro models that accurately replicate tumour behaviour. We present a concise overview of the intrahospital workflow for establishing patient-derived organoids and analyse the morphological and immunophenotypical features of high-grade serous carcinoma (HGSC), serous borderline tumour (SBT)/low-grade serous carcinoma (LGSC), and normal fallopian tube (FT) organoids.
Samples were collected from patients undergoing surgery or paracentesis. Tissue underwent mechanical and enzymatical digestion. Resulting cell suspensions were resuspended in an extracellular matrix substitute for subsequent culture. Despite the low efficacy in establishing HGSC organoids (n = 1/7, 14%; 96 days, 11 passages), we successfully established two organoid lines of SBT/LGSC (n = 2/2, 100%; 65 days, 7 passages; 134 days, 16 passages) and normal FT (n = 2/2, 100%; 73 days, 10 passages; 58 days, 8 passages). HGSC organoids exhibited limited growth and mostly irregular structures, while preserving the p53 immunostaining pattern of the original tumour. SBT/LGSC and FT organoids maintained features of architectural complexity and faithfully recapitulated the original immunoprofile.
This study highlights the need for a multidisciplinary collaboration in both clinical and research settings to establish patient-derived organoids. It emphasises the pivotal contribution of pathologists in meticulous sampling and organoid characterisation. The integration of diverse expertise is essential for maximising the potential of organoids as preclinical tools, advancing our understanding of tubo-ovarian carcinoma, and ultimately improving patient outcomes.
输卵管卵巢癌是妇科相关死亡的主要原因，具有显著的生物学和临床异质性。尽管药物研发取得了进展，但预测治疗效果仍然具有挑战性，部分原因是准确复制肿瘤行为的体外模型有限。我们简要概述了医院内建立患者来源类器官的工作流程，并分析了高级别浆液性癌（HGSC）、浆液性交界性肿瘤（SBT）/低级别浆液性癌（LGSC）和正常输卵管（FT）类器官的形态学和免疫表型特征。
样本取自接受手术或穿刺的患者。组织经过机械和酶消化。所得细胞悬液重悬于细胞外基质替代物中进行后续培养。尽管建立HGSC类器官的效率较低（n = 1/7，14%；96天，传代11次），但我们成功建立了两条SBT/LGSC类器官系（n = 2/2，100%；65天，传代7次；134天，传代16次）和正常FT类器官系（n = 2/2，100%；73天，传代10次；58天，传代8次）。HGSC类器官生长有限，结构大多不规则，同时保留了原发肿瘤的p53免疫染色模式。SBT/LGSC和FT类器官保持了结构复杂性特征，并忠实地重现了原始免疫谱。
本研究强调在临床和研究环境中建立患者来源类器官需要多学科合作。它强调了病理学家在细致采样和类器官表征方面的关键贡献。整合不同专业知识对于最大限度发挥类器官作为临床前工具的潜力、增进我们对输卵管卵巢癌的理解并最终改善患者预后至关重要。
