The Amount of Bifidobacterium Genus in Colorectal Carcinoma Tissue in Relation to Tumor Characteristics and Clinical Outcome.

Keisuke Kosumi, Tsuyoshi Hamada, Hideo Koh, Jennifer Borowsky, Susan Bullman, Tyler S Twombly, Daniel Nevo, Yohei Masugi, Li Liu, Annacarolina da Silva, Yang Chen, Chunxia Du, Mancang Gu, Chenxi Li, Wanwan Li, Hongli Liu, Yan Shi, Kosuke Mima, Mingyang Song, Katsuhiko Nosho, Jonathan A Nowak, Reiko Nishihara, Hideo Baba, Xuehong Zhang, Kana Wu, Molin Wang, Curtis Huttenhower, Wendy S Garrett, Matthew L Meyerson, Jochen K Lennerz, Marios Giannakis, Andrew T Chan, Jeffrey A Meyerhardt, Charles S Fuchs, Shuji Ogino

Journal: The American journal of pathology 2019;188(12):2839-2852

PMID: 30243655

Abstract

Evidence indicates a complex link between microbiota, tumor characteristics, and host immunity in the tumor microenvironment. In experimental studies, bifidobacteria appear to modulate intestinal epithelial cell differentiation. Accumulating evidence suggests that bifidobacteria may enhance the antitumor immunity and efficacy of immunotherapy. We hypothesized that the amount of bifidobacteria in colorectal carcinoma tissue might be associated with tumor differentiation and higher immune response to colorectal cancer. Using a molecular pathologic epidemiology database of 1313 rectal and colon cancers, we measured the amount of Bifidobacterium DNA in carcinoma tissue by a quantitative PCR assay. The multivariable regression model was used to adjust for potential confounders, including microsatellite instability status, CpG island methylator phenotype, long-interspersed nucleotide element-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Intratumor bifidobacteria were detected in 393 cases (30%). The amount of bifidobacteria was associated with the extent of signet ring cells (P = 0.002). Compared with Bifidobacterium-negative cases, multivariable odd ratios for the extent of signet ring cells were 1.29 (95% CI, 0.74-2.24) for Bifidobacterium-low cases and 1.87 (95% CI, 1.16-3.02) for Bifidobacterium-high cases (P = 0.01). The association between intratumor bifidobacteria and signet ring cells suggests a possible role of bifidobacteria in determining distinct tumor characteristics or as an indicator of dysfunctional mucosal barrier in colorectal cancer.

Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Address: Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Department of Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan.; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Department of Pathology, Center for Integrated Diagnostics, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts; Conjoint Gastroenterology Laboratory, Queensland Institute of Medical Research Berghofer, Brisbane, Queensland, Australia; School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts.; Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Department of Pathology, Center for Integrated Diagnostics, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts.; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.; Yale Cancer Center, New Haven, Connecticut; Department of Medicine, Yale School of Medicine, New Haven, Connecticut; Smilow Cancer Hospital, New Haven, Connecticut.; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: [email protected].
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