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

Løvig T, Andersen SN, Thorstensen L, Diep CB, Meling GI, Lothe RA, Rognum TO - Br. J. Cancer (2002)

Bottom Line: Improved survival has previously been found in patients with expression of HLA-DR antigens on their tumour cells.We confirmed that patients with strong positive HLA-DR staining had improved survival (P<0.001) compared to patients with no 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Forensic Medicine, The National Hospital, University of Oslo, 0027 Oslo, Norway. tone.loving@labmed.uio.no

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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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.
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fig2: 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.

Mentions: During the follow-up period of 10–13 years there were 138 cancer specific deaths in the group of 357 patients included in the study. Dukes' stage is significantly associated with patient survival (P<0.001, log rank test for trend). There is a better patient survival in MSI-H tumours compared to MSS/MSI-L tumours, as shown by both univariate Kaplan–Meier method (P=0.004, log rank test for trend) and by multivatiate analysis (HR 0.44, 95% CI: 0.20–0.96, data not shown). Analysis of survival according to HLA-DR in the whole group of patients showed significant differences between the three patterns of tumour HLA-DR expression (P<0.001) (Figure 2Figure 2


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

Løvig T, Andersen SN, Thorstensen L, Diep CB, Meling GI, Lothe RA, Rognum TO - Br. J. Cancer (2002)

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.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2364272&req=5

fig2: 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.
Mentions: During the follow-up period of 10–13 years there were 138 cancer specific deaths in the group of 357 patients included in the study. Dukes' stage is significantly associated with patient survival (P<0.001, log rank test for trend). There is a better patient survival in MSI-H tumours compared to MSS/MSI-L tumours, as shown by both univariate Kaplan–Meier method (P=0.004, log rank test for trend) and by multivatiate analysis (HR 0.44, 95% CI: 0.20–0.96, data not shown). Analysis of survival according to HLA-DR in the whole group of patients showed significant differences between the three patterns of tumour HLA-DR expression (P<0.001) (Figure 2Figure 2

Bottom Line: Improved survival has previously been found in patients with expression of HLA-DR antigens on their tumour cells.We confirmed that patients with strong positive HLA-DR staining had improved survival (P<0.001) compared to patients with no 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Forensic Medicine, The National Hospital, University of Oslo, 0027 Oslo, Norway. tone.loving@labmed.uio.no

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.

Show MeSH
Related in: MedlinePlus