title: Expression of major histocompatibility complex class I-related chain A/B (MICA/B) in pancreatic carcinoma.
abstract: Major histocompatibility complex class I-related chain A and B (MICA/B) are two stress-inducible ligands that bind to the immunoreceptor NKG2D and play an important role in mediating cytotoxicity of NK and T cells. Release of MIC molecules from the cell surface is thought to constitute an immune escape mechanism of tumor cells and thus could be associated with more aggressive course of tumor growth. In this study, we investigated the expression of MICA/B in ductal pancreatic carcinoma and serum in relation to tumor stage, differentiation and survival. MICA/B expression in tumor tissues and sera from patients with pancreatic cancer were analyzed by immunohistochemical staining (IHC), western blotting and ELISA, respectively. MICA/B expression was present in 17 of 22 (77%) of the tumors but not in normal pancreatic ductal epithelial cells. Poorly differentiated tumors showed more pronounced MICA/B expression compared to differentiated tumors, but did not correlate significantly to other tumor characteristics. MICA/B-negative tumors displayed significantly lower incidence of lymph node metastases (p<0.01), and less mortality within 3 years following resection (p<0.02). In conclusion, tissue levels of MICA/B expression were elevated in pancreatic cancer cells without elevated levels in serum, despite well-recognized acute phase reactants in serum. Poorly differentiated tumors showed high MICA/B expression, which was related to extended tumor lymph node metastases and less frequent long-term survival.
authors.affiliation: Department of Surgery and Institute for Research of Digestive System, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Zilvinas
authors.initials: Z
authors.lastname: Dambrauskas
authors.forename: Helena
authors.initials: H
authors.lastname: Svensson
authors.forename: Meghnad
authors.initials: M
authors.lastname: Joshi
authors.forename: Anders
authors.initials: A
authors.lastname: Hyltander
authors.forename: Peter
authors.initials: P
authors.lastname: Naredi
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Iresjö
mesh_terms: D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000097:blood; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D013601:T-Lymphocytes
chemical_list: D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; D036341:Intercellular Signaling Peptides and Proteins; C099187:MHC class I-related chain A; C098080:MICB antigen; C423230:ULBP2 protein, human