title: Strong HLA-DR expression in microsatellite stable carcinomas of the large bowel is associated with good prognosis.
abstract: Progression of colorectal cancer may follow either of two main genetic routes: the chromosome- or microsatellite-instability pathways. Association between the patients' prognosis and microsatellite instability has been questioned. Improved survival has previously been found in patients with expression of HLA-DR antigens on their tumour cells. In this study, the expression of HLA-DR antigen was investigated by immunohistochemistry in 357 large bowel carcinomas stratified by microsatellite instability status. Sixteen per cent of the tumours showed strong HLA-DR expression and 35% had weak DR expression. We confirmed that patients with strong positive HLA-DR staining had improved survival (P<0.001) compared to patients with no HLA-DR expression. Strong epithelial HLA-DR staining was significantly associated with high level of microsatellite instability (P<0.001). In the subgroup of tumours with characteristics typical of the chromosomal instability phenotype, i.e. in microsatellite-stable tumours, the patients positive for the HLA-DR determinants showed better survival than those without HLA-DR expression. The protective effect of HLA-DR expression on survival was confirmed by multivariate analysis, both in the whole patient group and in the microsatellite-stable/microsatellite instability-low group. This might be explained by enhanced T-cell mediated anti-tumour immune responses against tumour cells in the HLA-DR positive tumours. The finding of better patient survival in the subgroup of strong HLA-DR positive microsatellite-stable tumours may have clinical implications for these patients.
authors.affiliation: Institute of Forensic Medicine, The National Hospital, University of Oslo, 0027 Oslo, Norway. tone.loving@labmed.uio.no
authors.forename: T
authors.initials: T
authors.lastname: Løvig
authors.forename: S N
authors.initials: SN
authors.lastname: Andersen
authors.forename: L
authors.initials: L
authors.lastname: Thorstensen
authors.forename: C B
authors.initials: CB
authors.lastname: Diep
authors.forename: G I
authors.initials: GI
authors.lastname: Meling
authors.forename: R A
authors.initials: RA
authors.lastname: Lothe
authors.forename: T O
authors.initials: TO
authors.lastname: Rognum
mesh_terms: D000367:Age Factors; D000368:Aged; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004198:Disease Susceptibility; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012727:Sex Characteristics; D016019:Survival Analysis
chemical_list: D006684:HLA-DR Antigens