Andratschke M, Pauli C, Stein M, Chaubal S, Wollenberg B
ENT-Department, Grosshadern Medical Center, Ludwig-Maximilians-University of Munich, Germany.
Anticancer Res. 2003 Mar-Apr;23(2B):1467-71.
Although squamous cell carcinoma of the head and neck region very rarely metastasize to the skeleton, epithelial cells have been found in bone marrow aspirates of these patients. This observation reflects the general spread of the disease, indicating a poor clinical prognosis with a much higher risk of developing local or distant recurrences. In a first attempt to characterize the phenotypic properties, the expression of the major histo-compatibility complex (MHC) class I antigens on bone marrow micrometastases was assessed. It has been shown that the down-regulation of these molecules is a potential mechanism to escape from HLA class I restricted lysis by cytotoxic T-cells. The significance of reduced MHC class I expression might be relevant for the survival of residual metastatic cells in the bone marrow of patients with squamous cell carcinoma of the head and neck region. Bone marrow aspirates were screened for individual disseminated epithelial cells using the immunoalkaline phosphatase technique with monoclonal antibodies to the epithelial differentiation marker cytokeratin 19 (CK19), as described previously. Specimens containing CK19-positive cells were colabelled with the monoclonal antibody W6/32. The loss of MHC expression is not related to the tumor stage but clearly to the degree of differentiation: 6 out of 7 patients with low-grade SCCHN, but only 3 out of 13 patients with medium-grade SCCHN showed a complete loss of MHC class I molecules. This finding could indicate the reduced prognosis of undifferentiated SCCHN. The lack of MHC class I expression could encourage the survival of residual tumor cells in the bone marrow of patients with SCCHN that evade immunosurveillance.
尽管头颈部鳞状细胞癌极少转移至骨骼,但在这些患者的骨髓穿刺物中已发现上皮细胞。这一观察结果反映了疾病的广泛扩散,表明临床预后较差,局部或远处复发风险更高。在首次尝试表征表型特性时,评估了骨髓微转移灶上主要组织相容性复合体(MHC)I类抗原的表达。研究表明,这些分子的下调是逃避细胞毒性T细胞介导的HLA I类限制性裂解的潜在机制。MHC I类表达降低的意义可能与头颈部鳞状细胞癌患者骨髓中残留转移细胞的存活有关。如前所述,使用针对上皮分化标志物细胞角蛋白19(CK19)的单克隆抗体的免疫碱性磷酸酶技术,对头颈部鳞状细胞癌患者的骨髓穿刺物进行单个散在上皮细胞的筛查。含有CK19阳性细胞的标本与单克隆抗体W6/32进行共标记。MHC表达的缺失与肿瘤分期无关,但与分化程度明显相关:7例低级别头颈部鳞状细胞癌患者中有6例,但13例中级别头颈部鳞状细胞癌患者中只有3例显示MHC I类分子完全缺失。这一发现可能表明未分化头颈部鳞状细胞癌的预后较差。MHC I类表达的缺失可能会促使头颈部鳞状细胞癌患者骨髓中逃避免疫监视的残留肿瘤细胞存活。