Screening for Oral Precancer with Noninvasive Genetic Cytology
Screening for Oral Precancer with Noninvasive Genetic Cytology
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DOI：
10.1158/1940-6207.capr-08-0128
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发表时间：
2009-02-01
影响因子：
3.3
通讯作者：
Brakenhoff, Ruud H.
中科院分区：
文献类型：
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作者：
Bremmer, Jantine F.;Graveland, A. Peggy;Brakenhoff, Ruud H.
口腔鳞状细胞癌发生在癌前区，由基因改变的粘膜上皮细胞组成。这些癌前病变可能表现为临床可见的病变，特别是口腔白斑，但绝大多数临床无法检测到。本研究的目的是评估一种检测癌前病变的无创筛查方法的潜在价值。作为第一步，我们开发了一种合适的检测方法，并对25名白斑患者和20名非癌症对照进行了研究。用刷子从口腔黏膜的多个小区域去除脱落的细胞，包括白斑。使用已知在口腔癌前病变中频繁出现的微卫星标记，研究刷样中3p、9p、11q和17p染色体上的等位基因失衡（AI）。20例对照受试者的全部（137例）样本均不存在AI，特异性为100%。在所研究的白斑病变中，40%（25个中的10个）的脱落细胞样本中检测到AI。在白斑病变外也发现遗传改变。最常见的是AI（9 / 10）。无创检测与白斑病变的活检结果相对照，估计敏感性为78%(7 / 9)，阳性预测值为100%（7 / 7）。总之，这些结果表明了一种无创遗传筛查方法检测和监测口腔癌前病变的可行性。因此，该试验可能有助于口腔鳞状细胞癌的二级预防。该试验也显示出检测不可见的癌前病变的希望。
Oral squamous cell carcinomas develop in precancerous fields consisting of genetically altered mucosal epithelial cells. These precancerous fields may appear as clinically visible lesions, in particular, oral leukoplakia, but the large majority remains clinically undetectable. The aim of this study was to assess the potential value of a noninvasive screening approach to detect precancerous fields. As a first step, we developed a suitable assay and investigated 25 leukoplakia patients and 20 noncancer control subjects. Exfoliated cells were removed by a brush from multiple small areas of the oral mucosa, including the leukoplakia. Brushed samples were investigated for allelic imbalance (AI) at chromosomes 3p, 9p, 11q, and 17p using microsatellite markers known to show frequent alterations in oral precancer. AI was absent in all (137) of the samples of the 20 control subjects, yielding a specificity of 100%. AI was detected in exfoliated cell samples of 40% (10 of 25) of the leukoplakia lesions studied. Genetic changes were also found outside the leukoplakia lesions. Most frequent was AI at 9p (9 of 10). The noninvasive assay was validated against the biopsy results of the leukoplakia lesions yielding an estimate of sensitivity of 78% (7 of 9) and a positive predictive value of 100% (7 of 7). Altogether, these results show the feasibility of a noninvasive genetic screening approach for the detection and monitoring of oral precancer. This assay could therefore contribute to the secondary prevention of oral squamous cell carcinoma. The assay also shows promise for the detection of precancerous changes that are not macroscopically visible.