HLA class I expression and chromosomal deletions at 6p and 15q in head and neck squamous cell carcinomas
HLA class I expression and chromosomal deletions at 6p and 15q in head and neck squamous cell carcinomas
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DOI：
10.1034/j.1399-0039.1999.540304.x
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发表时间：
1999-09-01
期刊：
影响因子：
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通讯作者：
Tilanus, M
中科院分区：
文献类型：
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作者：
Feenstra, M;Veltkamp, M;Tilanus, M
染色体区域 6p21.3 缺失是头颈鳞状细胞癌 (HNSCC) 中的常见事件。由于人类白细胞抗原（HLA）复合物位于6p21.3，该区域杂合性缺失（LOH）可能为肿瘤细胞提供免疫逃逸肿瘤表型。在本研究中，我们研究了HLA I类、TAP1和TAP2表达与6p21.3处LOH的相关性。通过免疫组织化学方法分析 HLA I 类和 TAP1 和 TAPE 蛋白表达，使用位于 6p21.3 的 5 个微卫星标记（D6S105、D6S265、D6S276、D6S273、D6S291）和位于 6 号染色体着丝粒的 2 个标记，选择一组 41 个 HLA I 类表达下调的 HNSCC 进行 LOH 研究。 (D6S473) 和 6p 端粒 (D6S277)。此外，使用 beta(2)m 基因侧翼的 2 个微卫星标记（D15S126 和 D15S153）研究了 beta-2-微球蛋白 (beta(2)m) 基因的 LOH，并将其与 beta(2)m 和 HLA I 类表达相关。在 20/41 (49%) 的 HNSCC 中，发现 6p21.3 处至少有一个位点发生等位基因丢失。 β(2)m 表达下调的 4/10 (40%) HNSCC 和 HLA I 类表达下调的 12/41 (29%) HNSCC 中发现 15q 缺失。我们的数据表明，HLA I 类表达的下调与 HNSCC 中 6p21.3 处染色体区域的丢失相关，此外，10 对 DNA 样本中 6p21.3 和 15q 处的 LOH 也存在相关性。对源自原发性 HNSCC、淋巴结转移和外周血淋巴细胞 (PBL) 的细胞进行了研究。五（5/10）原发性肿瘤含有与相应淋巴结转移相同的缺失。其他病例在原发肿瘤（3 例）或淋巴结转移灶（1 例）中存在缺失，或者根本没有缺失（1 例）。
Loss at the chromosomal region 6p21.3 is a frequent event in head and neck squamous cell carcinomas (HNSCC). Since the human leukocyte antigen (HLA) complex is located at 6p21.3, loss of heterozygosity (LOH) of this region may provide tumour cells with an immune-escape tumour phenotype, In the present study, we have studied the correlation of HLA class I, TAP1 and TAP2 expression and LOH at 6p21.3. HLA class I and TAP1 and TAPE protein expression was analysed by immunohistochemical procedures, A panel of 41 HNSCC with downregulated HLA class I expression was selected for LOH studies using 5 microsatellite markers located at 6p21.3 (D6S105, D6S265, D6S276, D6S273, D6S291) and 2 markers located at the chromosome 6 centromere (D6S473) and the 6p telomere (D6S277). In addition, LOH of the beta-2-microglobulin (beta(2)m) gene was studied using 2 microsatellite markers flanking the beta(2)m gene (D15S126 and D15S153) and was correlated with beta(2)m and HLA class I expression. In 20/41 (49%) of the HNSCC, allelic loss for at least one locus at 6p21.3 was found. Loss at 15q was found in 4/10 (40%) HNSCC with downregulated beta(2)m expression and in 12/41 (29%) HNSCC with downregulated HLA class I expression. Our data show that downregulation of HLA class I expression is correlated with loss of chromosomal regions at 6p21.3 in HNSCC, In addition, LOH at 6p21.3 and 15q in 10 paired samples of DNA. derived from the primary HNSCC, the lymph node metastases and from peripheral blood lymphocytes (PBLs) was studied. Five (5/10) primary tumours contained the same deletion as the corresponding lymph node metastases. The other cases contained deletions either in the primary tumour (3 cases) or in the lymph node metastases (1 case) or no deletions at all (1 case).