DPC4 Gene Status of the Primary Carcinoma Correlates With Patterns of Failure in Patients With Pancreatic Cancer
DPC4 Gene Status of the Primary Carcinoma Correlates With Patterns of Failure in Patients With Pancreatic Cancer
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DOI：
10.1200/jco.2008.17.7188
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发表时间：
2009-04-10
影响因子：
45.3
通讯作者：
Laheru, Daniel
中科院分区：
文献类型：
--
作者：
Iacobuzio-Donahue, Christine A.;Fu, Baojin;Laheru, Daniel
目的与胰腺癌发生相关的大量资料相反，晚期胰腺癌（III期和IV期）的临床和分子特征尚不清楚。对死于疾病的胰腺癌患者进行的全面研究有可能极大地扩展我们对这种疾病最致命阶段的了解，并确定新的干预领域。材料和方法对76名有记录的胰腺癌患者进行快速尸检。终末期疾病的组织学特征进行了测定和相关的阶段在初步诊断，失败的模式（局部破坏V转移性疾病）和KRAS 2，TP 53，和DPC 4基因的状态。结果在尸检中，30%的患者死于局部破坏性胰腺癌，70%死于广泛的转移性疾病。尸检中发现的这些不同的失败模式（局部破坏性v转移性）与初始表现的临床分期、治疗史或组织病理学特征无关。然而，DPC 4免疫标记状态的癌组织收获尸检，DPC 4基因状态的敏感标志物，与广泛转移的存在高度相关，但不与局部破坏性肿瘤（P = .007）。在初次诊断时确定DPC 4状态可能对将患者分为与局部控制和全身治疗相关的治疗方案有价值。J Clin Oncol 27：1806-1813. (C)2009年美国临床肿瘤学会
PurposeContrary to the extensive data accumulated regarding pancreatic carcinogenesis, the clinical and molecular features characteristic of advanced stage (stage III and IV) disease are unknown. A comprehensive study of pancreatic cancers from patients who have succumbed to their disease has the potential to greatly expand our understanding of the most lethal stage of this disease and identify novel areas for intervention.Materials and MethodsRapid autopsies were performed on 76 patients with documented pancreatic cancer. The histologic features of end stage disease were determined and correlated to the stage at initial diagnosis, patterns of failure (locally destructive v metastatic disease) and the status of the KRAS2, TP53, and DPC4 genes.ResultsAt autopsy, 30% of patients died with locally destructive pancreatic cancer, and 70% died with widespread metastatic disease. These divergent patterns of failure found at autopsy (locally destructive v metastatic) were unrelated to clinical stage at initial presentation, treatment history, or histopathologic features. However, Dpc4 immunolabeling status of carcinoma tissues harvested at autopsy, a sensitive marker of DPC4 genetic status, was highly correlated with the presence of widespread metastasis but not with locally destructive tumors (P = .007).ConclusionPancreatic cancers are represented by distinct genetic subtypes with significantly different patterns of failure. Determinations of DPC4 status at initial diagnosis may be of value in stratifying patients into treatment regimens related to local control versus systemic therapy. J Clin Oncol 27: 1806-1813. (C) 2009 by American Society of Clinical Oncology