Background: Organoid cultures have received much attention in recent years due to the promise of patient-derived organoid cultures for exploration of personalized cancer treatment strategies. Organoid cultures have been established from a variety of malignancies; however, lack of a thorough histopathological analysis has limited the acceptance of organoid models as translational tools.Methods: Here, we aimed to establish patient-derived tumor-organoid (PDTO) models from human non-small-cell lung cancer (NSCLC) resection specimens and provide a thorough histopathological evaluation of the cultures.Results: We show that we were able to establish organoid cultures of lung adenocarcinomas (LUADs) and lung squamous cell carcinomas (LUSCs) successfully, and that the organoid cultures of different subtypes of NSCLC preserved the histoarchitecture and growth pattern of the tumors they derive from. Immunohistochemistry and AB-PAS staining confirmed the subtype-specific protein expression pattern and preserved mucin production in LUAD organoids. The genetic abnormalities of the tumors assessed by immunohistochemistry (IHC-P) were preserved in the organoid cultures.Conclusions: Our thorough study reveals conserved PDTO histopathology, supports further exploration, and encourages using PDTO models in translational research projects. PDTO models hold remarkable promise as patient-specific models and may be applied to predict therapy response in cases where molecular–pathological analyses pose significant management dilemmas, and they also may provide a platform for exploring the molecular mechanisms of therapy resistance in a biologically relevant model system.
背景：近年来，类器官培养因其在探索个性化癌症治疗策略方面的潜力而备受关注。目前多种恶性肿瘤已成功建立类器官培养体系，但由于缺乏系统的组织病理学分析，类器官模型作为转化医学工具的认可度仍受限制。 方法：本研究旨在利用人非小细胞肺癌（NSCLC）切除标本建立患者来源肿瘤类器官（PDTO）模型，并对培养体系进行系统的组织病理学评估。 结果：我们成功建立了肺腺癌（LUAD）和肺鳞癌（LUSC）的类器官培养体系，不同亚型NSCLC的类器官培养物均保留了来源肿瘤的组织结构和生长模式。免疫组织化学和AB-PAS染色证实LUAD类器官保持了亚型特异性蛋白表达模式及黏液分泌功能。通过免疫组化检测的肿瘤遗传异常特征在类器官培养体系中得以保留。 结论：本研究通过系统分析证实PDTO模型具有稳定的组织病理学特征，支持其进一步开发应用，并鼓励在转化研究项目中采用该模型。PDTO模型作为患者特异性模型具有显著潜力，既可在分子病理学分析面临重大诊疗困境时预测治疗反应，也能为在生物学相关模型系统中探索治疗耐药分子机制提供研究平台。
肿瘤(癌症)患者之家