title: Expression of the stress-related MHC class I chain-related protein MICA is an indicator of good prognosis in colorectal cancer patients.
abstract: The realization of targeted cancer therapy has driven the need to improve selection of patients with colorectal cancer for adjuvant therapy, leading to a search for potential new prognostic markers. There is accumulating evidence that immunosurveillance acts as an extrinsic tumor suppressor. As genetic instability is an early event in colorectal cancer, this can lead to altered expression of molecules conferring resistance to immune attack. Hence, molecules up or downregulated in this process may impact on patient survival. In our study, 449 colorectal tumors were screened for expression of the stress-related protein MICA, which functions as a ligand for the NKG2D receptor and whose expression confers susceptibility to both T- and NK-cell attack. Intensity of MICA expression was quantified using automated image analysis and MICA expression showed no correlation with conventional clinicopathological variables. In contrast, survival analysis showed a significant correlation between higher levels of MICA expression and improved disease-specific survival, with independent prognostic significance in multivariate analysis. Thus, patients with low levels of MICA and a poor prognosis may be good candidates for aggressive chemotherapy. In contrast, patients with high expression of MICA may be candidates for the antibody therapies, as they should be susceptible to NK killing by antibody dependent cellular cytotoxicity.
authors.affiliation: Academic Department of Clinical Oncology, University of Nottingham, City Hospital, Nottingham, United Kingdom. nicholas.watson@nottingham.ac.uk
authors.forename: Nicholas F S
authors.initials: NF
authors.lastname: Watson
authors.forename: Ian
authors.initials: I
authors.lastname: Spendlove
authors.forename: Zahra
authors.initials: Z
authors.lastname: Madjd
authors.forename: Roger
authors.initials: R
authors.lastname: McGilvray
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Green
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
authors.forename: John H
authors.initials: JH
authors.lastname: Scholefield
authors.forename: Lindy G
authors.initials: LG
authors.lastname: Durrant
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A