title: HLA class II antigen expression in colorectal carcinoma tumors as a favorable prognostic marker.
abstract: The goal of this study was to determine the frequency of HLA class II antigen expression in colorectal carcinoma (CRC) tumors, its association with the clinical course of the disease, and the underlying mechanism(s). Two tissue microarrays constructed with 220 and 778 CRC tumors were stained with HLA-DR, DQ, and DP antigen-specific monoclonal antibody LGII-612.14, using the immunoperoxidase staining technique. The immunohistochemical staining results were correlated with the clinical course of the disease. The functional role of HLA class II antigens expressed on CRC cells was analyzed by investigating their in vitro interactions with immune cells. HLA class II antigens were expressed in about 25% of the 220 and 21% of the 778 tumors analyzed with an overall frequency of 23%. HLA class II antigens were detected in 19% of colorectal adenomas. Importantly, the percentage of stained cells and the staining intensity were significantly lower than those detected in CRC tumors. However, HLA class II antigen staining was weakly detected only in 5.4% of 37 normal mucosa tissues. HLA class II antigen expression was associated with a favorable clinical course of the disease. In vitro stimulation with interferon gamma (IFNγ) induced HLA class II antigen expression on two of the four CRC cell lines tested. HLA class II antigen expression on CRC cells triggered interleukin-1β (IL-1β) production by resting monocytes. HLA class II antigen expression in CRC tumors is a favorable prognostic marker. This association may reflect stimulation of IL-1β production by monocytes.
authors.affiliation: Laboratory of Tumor Immunology and Immunotherapy, Institute of Translational Pharmacology, Department of Medicine, CNR, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sconocchia
authors.affiliation: Institute of Pathology, University of Basel, Basel, Switzerland.
authors.forename: Serenella
authors.initials: S
authors.lastname: Eppenberger-Castori
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Inti
authors.initials: I
authors.lastname: Zlobec
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland ; First Department of Pathology, Medical School, University of Athens, Athens, Greece.
authors.forename: Eva
authors.initials: E
authors.lastname: Karamitopoulou
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Arriga
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Coppola
authors.affiliation: Laboratory of Tumor Immunology and Immunotherapy, Institute of Translational Pharmacology, Department of Medicine, CNR, Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Caratelli
authors.affiliation: Institute for Surgical Research and Hospital Management, University of Basel, Basel, Switzerland.
authors.forename: Giulio Cesare
authors.initials: GC
authors.lastname: Spagnoli
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Lauro
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lugli
authors.affiliation: Institute for Surgical Research and Hospital Management, University of Basel, Basel, Switzerland ; Department of Gastroenterology, Shangai East Hospital, Tongji University, Shangai, PR China.
authors.forename: Junyi
authors.initials: J
authors.lastname: Han
authors.affiliation: Institute for Surgical Research and Hospital Management, University of Basel, Basel, Switzerland.
authors.forename: Giandomenica
authors.initials: G
authors.lastname: Iezzi
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ferrone
authors.affiliation: Department of Biopathology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Amedeo
authors.initials: A
authors.lastname: Ferlosio
authors.affiliation: Institute of Pathology, University of Basel, Basel, Switzerland.
authors.forename: Luigi
authors.initials: L
authors.lastname: Tornillo
authors.affiliation: Institute for Surgical Research and Hospital Management, University of Basel, Basel, Switzerland.
authors.forename: Raoul
authors.initials: R
authors.lastname: Droeser
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Rossi
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Attanasio
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Soldano
authors.initials: S
authors.lastname: Ferrone
authors.affiliation: Institute of Pathology, University of Basel, Basel, Switzerland.
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
mesh_terms: D002277:Carcinoma / Q000175:diagnosis* / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006682:HLA-DP Antigens / Q000378:metabolism; D006683:HLA-DQ Antigens / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis
chemical_list: D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D053583:Interleukin-1beta; D015850:Interleukin-6; D007371:Interferon-gamma