Spafford M F, Koch W M, Reed A L, Califano J A, Xu L H, Eisenberger C F, Yip L, Leong P L, Wu L, Liu S X, Jerónimo C, Westra W H, Sidransky D
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Clin Cancer Res. 2001 Mar;7(3):607-12.
Prompt detection of head and neck squamous cell carcinoma (HNSCC) is vital to successful patient management. In this feasibility study, we used microsatellite analysis to detect tumor-specific genetic alterations in exfoliated oral mucosal cell samples from patients with known cancer. Exfoliated mucosal cells in pretreatment oral rinse and swab samples were collected from 44 HNSCC patients and from 43 healthy control subjects (20 nonsmokers and 23 smokers). We tested a panel of 23 informative microsatellite markers to assay DNA from the matched lymphocyte, tumor (from cancer cases), and oral test samples. Loss of heterozygosity or microsatellite instability of at least one marker was detected in 38 (86%) of 44 primary tumors. Identical alterations were found in the saliva samples in 35 of these 38 cases (92% of those with markers; 79% overall) including 12 of 13 cases with small primaries [stage Tt or Tx (occult primary)] and 4 of 4 cases of patients that had undergone prior radiation. Microsatellite instability was detectable in the saliva in 24 (96%) of 25 cases in which it was present in the tumor, and loss of heterozygosity was identified in the test sample in 19 (61%) of 31 cases. No microsatellite alterations were detected in any of the samples from the healthy control subjects. This approach must now be refined and validated for the detection of clinically occult disease. Microsatellite analysis of oral samples may then become a valuable method for detecting and monitoring HNSCC.
对头颈部鳞状细胞癌（HNSCC）进行及时检测对于患者的成功治疗至关重要。在这项可行性研究中，我们使用微卫星分析来检测已知癌症患者脱落口腔黏膜细胞样本中的肿瘤特异性基因改变。从44例HNSCC患者以及43名健康对照者（20名不吸烟者和23名吸烟者）的预处理口腔冲洗液和拭子样本中收集脱落的黏膜细胞。我们检测了一组23个信息丰富的微卫星标记，以分析来自匹配的淋巴细胞、肿瘤（癌症病例）和口腔检测样本的DNA。在44例原发性肿瘤中的38例（86%）中检测到至少一个标记的杂合性缺失或微卫星不稳定性。在这38例中的35例（有标记病例的92%；总体的79%）唾液样本中发现了相同的改变，包括13例小原发性肿瘤[T1期或Tx期（隐匿性原发性肿瘤）]中的12例以及4例曾接受过放疗患者中的4例。在肿瘤中存在微卫星不稳定性的25例中的24例（96%）唾液中可检测到微卫星不稳定性，在31例中的19例（61%）检测样本中发现了杂合性缺失。在健康对照者的任何样本中均未检测到微卫星改变。这种方法现在必须进一步完善并验证用于检测临床隐匿性疾病。口腔样本的微卫星分析随后可能成为检测和监测HNSCC的一种有价值的方法。
