Strong HLA-DR expression in microsatellite stable carcinomas of the large bowel is associated with good prognosis - PubMed (original) (raw)

Strong HLA-DR expression in microsatellite stable carcinomas of the large bowel is associated with good prognosis

T Løvig et al. Br J Cancer. 2002.

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.

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Figures

Figure 1

Moderately differentiated large bowel carcinoma with strong HLA-DR expression. (A) HAS staining and (B) adjacent section stained green for HLA-DR determinants.

Figure 2

Survival analyses (cancer-related Kaplan–Meier plots) of patients with different degrees of HLA-DR expression. _n_=58 with strong DR expression, _n_=123 with weak DR expression and _n_=176 DR negative.

Figure 3

Survival analysis (cancer-related Kaplan–Meier plots) of patients in relation to HLA-DR expression and different variables. (A) Patients with MSS/MSI-L tumours, (B) patients with aneuploid tumours and (C) patients with moderately differentiated tumours. When considering strong DR expression compared to no expression, the _P_-value for MSS/MSI-L tumours was _P_=0.0024, _P_=0.0050 for aneuploid tumours, and _P_=0.0006 for moderately differentiated tumours.

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Strong HLA-DR expression in microsatellite stable carcinomas of the large bowel is associated with good prognosis - PubMed (original) (raw)