Potievskiy Mikhail B, Nekrasova Lidia A, Korobov Ivan V, Bykova Ekaterina A, Moshurov Ruslan I, Sokolov Pavel V, Shatalov Peter A, Falaleeva Natalia A, Petrov Leonid O, Trifanov Vladimir S, Ivanov Sergey A, Shegai Peter V, Kaprin Andrei D
FSBI National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 249036 Obninsk, Russia.
Department of Oncology and Radiology, Institute of Medicine, Peoples' Friendship University of Russia-RUDN University, 6 Miklukho-Maklaya Street, 117198 Moscow, Russia.
Life (Basel). 2025 Apr 11;15(4):635. doi: 10.3390/life15040635.
Pancreatic cancer is a tumor with a poor prognosis, and improving its survival outcomes remains a formidable challenge, requiring a multidisciplinary approach that integrates innovative surgical and pharmacological strategies, guided by molecular and genetic insights. The pathomorphological and genetic characteristics of pancreatic cancer, reflected in morphological, immunohistochemical, and serological marker expression, reveal key patterns of tumor genotypic changes during carcinogenesis, aiding in prognostic evaluation and clinical strategy development. The mutational profile of pancreatic tumors is quite heterogeneous and diverse in terms of mutated genes, including in relation to morphological subtypes, but certain patterns have been identified as a result of studies. Pancreatic adenocarcinoma, for instance, is frequently driven by mutations regulating cell division (KRAS). The disease prognosis often depends on the morphological subtype and tumor microenvironment. Neuroendocrine tumors of the pancreas are characterized by a number of pathogenetic features that distinguish them from adenocarcinomas. Thus, neuroendocrine tumors are characterized by mutations of the MENIN protein, which prevents cells from entering the mitosis phase by stimulating the expression of cell cycle regulators. Thus, epithelial and neuroendocrine malignancies of the pancreas differ in immunohistochemical and genetic features, but there are similar mechanisms of pathogenesis, such as BRCA1 and BRCA2 gene mutations, impaired expression of p53 antioncogene, and HIF-2α and mTOR receptor mutations. The predictive impact of serological markers, such as CA 19-9 and CEA, offers insights into tumor metastasis and long-term outcomes, emphasizing the need for personalized therapeutic strategies. Tailoring treatments based on individual molecular profiles holds promise for improving prognosis, as the genetic landscape of pancreatic tumors varies significantly between patients. This underscores the importance of a systematic, patient-specific approach that addresses tumor heterogeneity, resistance mechanisms, and the molecular underpinnings of carcinogenesis.
胰腺癌是一种预后较差的肿瘤，改善其生存结果仍然是一项艰巨的挑战，需要一种多学科方法，该方法整合创新的手术和药理学策略，并以分子和遗传学见解为指导。胰腺癌的病理形态学和遗传学特征反映在形态学、免疫组织化学和血清学标志物表达中，揭示了癌变过程中肿瘤基因型变化的关键模式，有助于预后评估和临床策略制定。胰腺肿瘤的突变谱在突变基因方面非常异质和多样，包括与形态学亚型相关的方面，但研究已经确定了某些模式。例如，胰腺腺癌经常由调节细胞分裂的突变（KRAS）驱动。疾病预后通常取决于形态学亚型和肿瘤微环境。胰腺神经内分泌肿瘤具有许多使其与腺癌区分开来的致病特征。因此，神经内分泌肿瘤的特征是MENIN蛋白突变，该突变通过刺激细胞周期调节因子的表达来阻止细胞进入有丝分裂期。因此，胰腺的上皮性和神经内分泌恶性肿瘤在免疫组织化学和遗传学特征上有所不同，但存在相似的发病机制，如BRCA1和BRCA2基因突变、p53抑癌基因表达受损以及HIF-2α和mTOR受体突变。血清学标志物如CA 19-9和CEA的预测影响为肿瘤转移和长期结果提供了见解，强调了个性化治疗策略的必要性。根据个体分子谱定制治疗有望改善预后，因为胰腺肿瘤的基因格局在患者之间差异很大。这凸显了一种系统的、针对患者的方法的重要性，该方法解决肿瘤异质性、耐药机制和癌变的分子基础。
