title: Associations between selected biomarkers and prognosis in a population-based pancreatic cancer tissue microarray.
abstract: 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.
authors.affiliation: Tissue Array Research Program, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-8316, USA.
authors.forename: Mikiko
authors.initials: M
authors.lastname: Takikita
authors.forename: Sean
authors.initials: S
authors.lastname: Altekruse
authors.forename: Charles F
authors.initials: CF
authors.lastname: Lynch
authors.forename: Mark T
authors.initials: MT
authors.lastname: Goodman
authors.forename: Brenda Y
authors.initials: BY
authors.lastname: Hernandez
authors.forename: Mark
authors.initials: M
authors.lastname: Green
authors.forename: Wendy
authors.initials: W
authors.lastname: Cozen
authors.forename: Myles
authors.initials: M
authors.lastname: Cockburn
authors.forename: Maria
authors.initials: M
authors.lastname: Sibug Saber
authors.forename: Marie
authors.initials: M
authors.lastname: Topor
authors.forename: Chris
authors.initials: C
authors.lastname: Zeruto
authors.forename: Behnoush
authors.initials: B
authors.lastname: Abedi-Ardekani
authors.forename: Marsha E
authors.initials: ME
authors.lastname: Reichman
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D015331:Cohort Studies; D006254:Hawaii / Q000453:epidemiology; D006801:Humans; D007150:Immunohistochemistry; D007484:Iowa / Q000453:epidemiology; D015141:Los Angeles / Q000453:epidemiology; D046228:Microarray Analysis; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D012042:Registries
chemical_list: D014408:Biomarkers, Tumor