免疫组化标志物在胰腺导管腺癌临床评估中的应用进展

Advances in the Application of Immunohistochemical Markers in the Clinical Evaluation of Pancreatic Ductal Adenocarcinoma

摘要: 胰腺导管腺癌(pancreatic ductal adenocarcinoma, PDAC)是恶性程度最高的消化系统肿瘤之一，侵袭性强，生物学异质性极大，故而现有手段尚难以充分获得患者生存获益。因此，更准确的肿瘤评估及更好的风险分层是推进个体化治疗的前提。免疫组化(immunohistochemistry, IHC)由于可及性好，又对常规病理标本有极好的适用性，在胰腺癌临床管理中已有基础而重要的地位，近年来已从传统的诊断支持技术自然、合理地拓展到预后评估及治疗反应预测领域。近年来学界对PDAC中多种免疫组化标志物的临床价值已有十分系统、充分的讨论，明确指出多指标联合检测有利于提高良恶性病变的鉴别能力，也有利于确定肿瘤来源。更重要的是，与细胞增殖、抑癌通路异常、上皮–间质转化及肿瘤免疫微环境相关的蛋白表达模式在风险评估中已有很好的应用前景。与此形成极好补充的是，免疫相关及分子替代指标正在成为筛选潜在治疗获益人群的新方向。然而，由于目前多数标志物尚无统一检测标准，故现有研究结果有明显异质性，单一指标又不能充分反映PDAC复杂的生物学本质，因此可以很自然、妥帖地预期今后的发展方向是构建多参数整合模型，把免疫组化、分子检测及数字病理技术三者深度融合，由此建立真正精准、临床可操作的综合评估体系。本文对免疫组化标志物在胰腺导管腺癌中的临床应用作了十分清楚、有层次的综述，先总结其在诊断鉴别、预后分层、治疗相关预测诸方面的研究进展，再自然、妥帖地讨论现存问题及今后方向，对胰腺癌的精准管理有极好启示。

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors in the digestive system, with strong invasiveness and significant biological heterogeneity. Therefore, current treatment methods have not been able to fully benefit patients in terms of survival. Thus, more accurate tumor assessment and better risk stratification are prerequisites for advancing personalized treatment. Immunohistochemistry (IHC) has a fundamental and important position in the clinical management of pancreatic cancer due to its good accessibility and excellent applicability to routine pathological specimens. In recent years, it has naturally and reasonably expanded from a traditional diagnostic support technique to the fields of prognosis assessment and treatment response prediction. In recent years, the academic community has had a very systematic and thorough discussion on the clinical value of multiple IHC markers in PDAC, clearly indicating that the combined detection of multiple indicators is beneficial for improving the ability to distinguish between benign and malignant lesions and determining the tumor origin. More importantly, protein expression patterns related to cell proliferation, abnormal tumor suppressor pathways, epithelial-mesenchymal transition, and the tumor immune microenvironment have shown good application prospects in risk assessment. Complementing this, immune-related and molecular surrogate markers are becoming new directions for screening potential treatment-benefited populations. However, due to the lack of unified detection standards for most of the current biomarkers, the existing research results show significant heterogeneity. Moreover, a single indicator cannot fully reflect the complex biological nature of PDAC. Therefore, it is quite natural and appropriate to expect that the future development direction will be to build a multi-parameter integrated model, deeply integrating immunohistochemistry, molecular detection, and digital pathology technologies, thereby establishing a truly precise and clinically operable comprehensive assessment system. This article provides a very clear and well-structured review of the clinical application of immunohistochemical markers in pancreatic ductal adenocarcinoma. It first summarizes the research progress in diagnosis and differentiation, prognosis stratification, and treatment-related prediction, and then naturally and appropriately discusses the existing problems and future directions. It offers excellent guidance for the precise management of pancreatic cancer.