Associations between selected biomarkers and prognosis in a population-based pancreatic cancer tissue microarray.
Associations between selected biomarkers and prognosis in a population-based pancreatic cancer tissue microarray.
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DOI：
10.1158/0008-5472.can-08-3879
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发表时间：
2009-04-01
期刊：
影响因子：
11.2
通讯作者：
Hewitt SM
中科院分区：
文献类型：
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作者：
Takikita M;Altekruse S;Lynch CF;Goodman MT;Hernandez BY;Green M;Cozen W;Cockburn M;Sibug Saber M;Topor M;Zeruto C;Abedi-Ardekani B;Reichman ME;Hewitt SM
胰腺癌是美国癌症死亡的第四大原因。缺乏预后生物标志物，治疗对生存的影响有限。使用来自监测、流行病学和最终结果登记处（爱荷华州、夏威夷和洛杉矶）的组织构建161例胰腺肿瘤（113例切除和48例活检）的组织微阵列。按年龄、种族、性别、分期、诊断时间段和治疗调整的比例风险模型。检查了标记物（MUC 1、MUC 2、MUC 5AC、突触素、嗜铬粒蛋白、神经元特异性烯醇化酶、表皮生长因子受体、HER 2、CD 5、CD 138、CK 5/6、CK 19、CK 20和p53）与诊断后生存时间之间的相关性。在调整协变量后，三种粘蛋白（MUC 1，MUC 2和MUC 5AC）的表达与较短的生存时间之间存在边缘统计学显著性相关。154例（96%）腺癌，特别是120例（75%）高分化至中等分化的导管腺癌，这种肿瘤类型在白色病例中比其他种族起源的病例更常见（P < 0.01）。对于分化型导管腺癌，观察到所有三种粘蛋白联合表达与其他粘蛋白表达模式（校正风险比，1.8; 95%置信区间，1.2-2.6）和MUC 2（+）与MUC 2（-）表达（校正风险比，1.6; 95%置信区间，1.1-2.4）的生存期较短。粘蛋白基因表达，特别是MUC 2表达，可能对分化型腺癌有预后价值。该队列和日本队列的肿瘤组织学不同。组织微阵列可用于评估其他生物标志物。基于组织的监测可用于监测人群中的肿瘤组织学，并促进应用研究。
Pancreatic cancer is the fourth leading cause of cancer death in the United States. Prognostic biomarkers are lacking, and treatment has limited effect on survival. Tissues from Surveillance, Epidemiology, and End Results registries (Iowa, Hawaii, and Los Angeles) were used to build a tissue microarray of 161 pancreatic tumors (113 resections and 48 biopsies). Proportional hazard models adjusted for age, race, sex, stage, time-period of diagnosis, and treatment. Associations were examined between markers (MUC1, MUC2, MUC5AC, synaptophysin, chromogranin, neuron specific enolase, epidermal growth factor receptor, HER2, CD5, CD138, CK5/6, CK19, CK20, and p53) and survival time from diagnosis. After adjusting for covariates, borderline statistically significant associations were seen between expression of each of the three mucins (MUC1, MUC2, and MUC5AC) and shorter survival time. The associations strengthened for 154 (96%) adenocarcinomas, particularly the 120 (75%) well-differentiated to moderately differentiated ductal adenocarcinomas, a tumor type that occurred more often in the cohort among White cases than cases of other racial origin (P < 0.01). For differentiated ductal adenocarcinomas, associations with shorter survival time were seen for expression of all three mucins combined versus other mucin expression patterns (adjusted hazard ratio, 1.8; 95% confidence interval, 1.2–2.6) and for MUC2(+) versus MUC2(−) expression (adjusted hazard ratio, 1.6; 95% confidence interval, 1.1–2.4). Mucin gene expression, particularly MUC2 expression, may have prognostic value for differentiated adenocarcinomas. Tumor histologies differed in this and Japanese cohorts. The tissue microarray is available to evaluate other biomarkers. Tissue-based surveillance can be used to monitor tumor histology in populations and facilitate applied research.