Feenstra M, Veltkamp M, van Kuik J, Wiertsema S, Slootweg P, van den Tweel J, de Weger R, Tilanus M
Department of Pathology, University Hospital, Utrecht, The Netherlands.
Tissue Antigens. 1999 Sep;54(3):235-45. doi: 10.1034/j.1399-0039.1999.540304.x.
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 TAP2 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-nmicroglobulin (beta2m) gene was studied using 2 microsatellite markers flanking the beta2m gene (D15S126 and D15S153) and was correlated with beta2m 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 beta2m 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).
6p21.3染色体区域缺失在头颈部鳞状细胞癌(HNSCC)中是常见事件。由于人类白细胞抗原(HLA)复合体位于6p21.3,该区域的杂合性缺失(LOH)可能赋予肿瘤细胞免疫逃逸的肿瘤表型。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、TAP1和TAP2蛋白表达。选择一组41例HLA I类表达下调的HNSCC进行LOH研究,使用位于6p21.3的5个微卫星标记(D6S105、D6S265、D6S276、D6S273、D6S291)以及位于6号染色体着丝粒(D6S473)和6p端粒(D6S277)的2个标记。此外,使用位于β2微球蛋白(β2m)基因两侧的2个微卫星标记(D15S126和D15S153)研究β2m基因的LOH,并将其与β2m和HLA I类表达相关联。在41例HNSCC中的20例(49%)中,发现6p21.3处至少一个位点存在等位基因缺失。在10例β2m表达下调的HNSCC中的4例(40%)以及41例HLA I类表达下调的HNSCC中的12例(29%)中发现15q缺失。我们的数据表明,HLA I类表达下调与HNSCC中6p21.3染色体区域缺失相关。此外,研究了来自原发性HNSCC、淋巴结转移灶和外周血淋巴细胞(PBL)的10对DNA样本中6p21.3和15q处的LOH。5例(5/10)原发性肿瘤与相应的淋巴结转移灶存在相同的缺失。其他病例中,有的在原发性肿瘤中存在缺失(3例),有的在淋巴结转移灶中存在缺失(1例),或者根本没有缺失(1例)。