Takikita Mikiko, Altekruse Sean, Lynch Charles F, Goodman Mark T, Hernandez Brenda Y, Green Mark, Cozen Wendy, Cockburn Myles, Sibug Saber Maria, Topor Marie, Zeruto Chris, Abedi-Ardekani Behnoush, Reichman Marsha E, Hewitt Stephen M
Tissue Array Research Program, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-8316, USA.
Cancer Res. 2009 Apr 1;69(7):2950-5. doi: 10.1158/0008-5472.CAN-08-3879. Epub 2009 Mar 10.
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.
胰腺癌是美国癌症死亡的第四大主要原因。目前缺乏预后生物标志物,且治疗对生存率的影响有限。利用监测、流行病学和最终结果登记处(爱荷华州、夏威夷州和洛杉矶)的组织构建了一个包含161个胰腺肿瘤(113例切除术和48例活检)的组织微阵列。比例风险模型根据年龄、种族、性别、分期、诊断时间和治疗进行了调整。研究了标志物(MUC1、MUC2、MUC5AC、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、HER2、CD5、CD138、CK5/6、CK19、CK20和p53)与诊断后的生存时间之间的关联。在调整协变量后,三种粘蛋白(MUC1、MUC2和MUC5AC)中每一种的表达与较短的生存时间之间存在边缘统计学显著关联。在154例(96%)腺癌中,这种关联更为明显,尤其是120例(75%)高分化至中分化导管腺癌,在该队列中,白人病例中的这种肿瘤类型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,三种粘蛋白联合表达与其他粘蛋白表达模式相比(调整后的风险比,1.8;95%置信区间,1.2 - 2.6)以及MUC2(+)与MUC2(-)表达相比(调整后的风险比,1.6;95%置信区间,1.1 - 2.4),均与较短的生存时间相关。粘蛋白基因表达,尤其是MUC2表达,可能对分化型腺癌具有预后价值。该队列与日本队列的肿瘤组织学存在差异。该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。