title: Tumor eosinophil infiltration and improved survival of colorectal cancer patients: Iowa Women's Health Study.
abstract: The role of the innate immune response in colorectal cancer is understudied. We examined the survival of colorectal cancer patients in relation to eosinophils, innate immune cells, infiltrating the tumor. Tissue microarrays were constructed from paraffin-embedded tumor tissues collected between 1986 and 2002 from 441 post-menopausal women diagnosed with colorectal cancer in the Iowa Women's Health Study. Tissue microarrays were stained with an eosinophil peroxidase antibody. Eosinophils in epithelial and stromal tissues within the tumor (called epithelial and stromal eosinophils, hereafter) were counted and scored into three and four categories, respectively. In addition, the degree of eosinophil degranulation (across epithelial and stromal tissues combined) was quantified and similarly categorized. We used Cox regression to estimate the hazard ratios and 95% confidence interval for all-cause and colorectal cancer death during 5-year follow-up after diagnosis and during follow-up through 2011 ('total follow-up'). The hazard ratios associated with eosinophil scores were adjusted for age of diagnosis, SEER (Surveillance, Epidemiology, and End Results) stage, tumor grade, body mass, and smoking history. High tumor stromal eosinophil score was inversely correlated with age and stage, and was associated with a decreased risk for all-cause and colorectal cancer death: hazard ratios (95% confidence intervals) were 0.61 (0.36-1.02; P-trend=0.02) and 0.48 (0.24-0.93; P-trend=0.01), respectively, during the 5-year follow-up for the highest vs lowest category. The inverse associations also existed for total follow-up for all-cause and colorectal cancer death for the highest vs lowest stromal eosinophil score: hazard ratios (95% confidence intervals) were 0.72 (0.48-1.08; P-trend=0.04) and 0.61 (0.34-1.12; P-trend=0.04), respectively. Further adjustment for treatment, comorbidities, additional lifestyle factors, tumor location, or molecular markers did not markedly change the associations, while adjustment for cytotoxic T cells slightly attenuated all associations. The infiltration of tumors with eosinophils, especially in stromal tissue, may be an important prognostic factor in colorectal cancer.
authors.affiliation: Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA.|University of Minnesota Masonic Cancer Center, Minneapolis, MN, USA.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Prizment
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Smyrk
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Lori S
authors.initials: LS
authors.lastname: Tillmans
authors.affiliation: Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: College of Veterinary Medicine, University of Minnesota, Saint Paul, MN, USA.
authors.forename: P
authors.initials: P
authors.lastname: Sriramarao
authors.affiliation: Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA.|University of Minnesota Masonic Cancer Center, Minneapolis, MN, USA.
authors.forename: Heather H
authors.initials: HH
authors.lastname: Nelson
authors.affiliation: Department of Epidemiology, University of Iowa, Iowa City, IA, USA.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Lynch
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
authors.affiliation: Division of Environmental Health Sciences, University of Minnesota School of Public Health, Minneapolis, MN, USA.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Church
authors.affiliation: Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.affiliation: Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA.|University of Minnesota Masonic Cancer Center, Minneapolis, MN, USA.
authors.forename: Kristin E
authors.initials: KE
authors.lastname: Anderson
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Limburg
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D006801:Humans; D007484:Iowa; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D016016:Proportional Hazards Models