title: Unique ectopic lymph node-like structures present in human primary colorectal carcinoma are identified by immune gene array profiling.
abstract: We hypothesized that immune gene-related signatures would predict the presence of unique histological features of lymphoid cell infiltrates in colorectal carcinoma (CRC) that correlate with clinical parameters. Metagene analysis with gene chip technology was performed on 326 CRCs, which were then sorted by low versus high gene scores. Microscopically, CRCs with a high gene score revealed a marked host immune response organized, remarkably, as lymphoid follicles. Proliferation involved both B and T cells. In every case, the presence of CD79a(+) B-cell precursors was identified, suggesting that the lymphoid follicles represent newly formed, ectopic lymph node-like structures. CD21(+) dendritic cells were present within the follicular germinal centers, and CD3(+) T cells were localized mainly in the parafollicular cortex zone surrounding the B-cell area of the follicles. A strong correlation between a 12-chemokine gene subset of the molecular profile and the presence of ectopic lymph node-like structures was associated with better patient survival independent of tumor staging, site location, microsatellite instability or stability, and patient treatment. These findings suggest beneficial, intratumoral immune cell priming and raise the possibility of immunotherapy intervention decisions based on molecular signatures that can identify the presence of tumor-localized, ectopic lymph node-like structures.
authors.affiliation: Anatomic Pathology Division, Moffitt Cancer Center, Tampa, FL 33612-9497, USA.
authors.forename: Domenico
authors.initials: D
authors.lastname: Coppola
authors.forename: Michael
authors.initials: M
authors.lastname: Nebozhyn
authors.forename: Farah
authors.initials: F
authors.lastname: Khalil
authors.forename: Hongyue
authors.initials: H
authors.lastname: Dai
authors.forename: Timothy
authors.initials: T
authors.lastname: Yeatman
authors.forename: Andrey
authors.initials: A
authors.lastname: Loboda
authors.forename: James J
authors.initials: JJ
authors.lastname: Mulé
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000556:secondary / Q000628:therapy; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D051925:CD79 Antigens / Q000276:immunology / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000276:immunology* / Q000628:therapy; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000276:immunology* / Q000556:secondary / Q000628:therapy; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology*; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D051925:CD79 Antigens; D012333:RNA, Messenger