Strong HLA-DR expression in microsatellite stable carcinomas of the large bowel is associated with good prognosis.
Strong HLA-DR expression in microsatellite stable carcinomas of the large bowel is associated with good prognosis.
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DOI：
10.1038/sj.bjc.6600507
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发表时间：
2002-09-23
影响因子：
8.8
通讯作者：
Rognum, T O
中科院分区：
文献类型：
--
作者：
Lovig, T;Andersen, S N;Thorstensen, L;Diep, C B;Meling, G I;Lothe, R A;Rognum, T O
结直肠癌的进展可能遵循两条主要遗传途径之一：染色体不稳定途径或微卫星不稳定途径。患者的预后与微卫星不稳定性之间的关系一直受到质疑。以前已经发现，肿瘤细胞上表达HLA-DR抗原的患者存活率有所提高。本研究采用免疫组织化学方法检测了357例大肠癌组织中人类白细胞抗原-DR的表达。16%的肿瘤显示出强的HLA-DR表达，35%的肿瘤有弱的DR表达。我们证实，与不表达HLADR的患者相比，HLADR强阳性患者的存活率有所提高(P<；0.001)。上皮性HLADR的强染色与高水平的微卫星不稳定性显著相关(P<；0.001)。在具有典型染色体不稳定表型特征的肿瘤亚群中，即在微卫星稳定型肿瘤中，人类白细胞抗原DR决定簇阳性的患者比不表达人类白细胞抗原DR决定簇的患者有更好的生存率。多因素分析证实，在整个患者组和微卫星稳定/微卫星不稳定-低组中，人类白细胞抗原-DR的表达对生存的保护作用。这可能是由于人类白细胞抗原DR阳性肿瘤中T细胞介导的抗肿瘤免疫反应增强所致。在人类白细胞抗原-DR阳性的微卫星稳定型肿瘤中发现较好的患者存活率可能对这些患者具有临床意义。《英国癌症杂志》(2002)87,756-762。DOI：10.1038/sj.bjc.6600507 www.bjancer.com2002英国癌症研究中心
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. British Journal of Cancer (2002) 87, 756–762. doi:10.1038/sj.bjc.6600507 www.bjcancer.com © 2002 Cancer Research UK