Potential use of quantitative tissue phenotype to predict malignant risk for oral premalignant lesions
Potential use of quantitative tissue phenotype to predict malignant risk for oral premalignant lesions
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DOI：
10.1158/0008-5472.can-07-2113
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发表时间：
2008-05-01
期刊：
影响因子：
11.2
通讯作者：
MacAulay, Calum
中科院分区：
文献类型：
--
作者：
Guillaud, Martial;Zhang, Lewei;MacAulay, Calum
早期诊断对降低口腔鳞状细胞癌（SCC）的发病率和死亡率的重要性早已被认识。然而，早期诊断的一个主要挑战是我们区分口腔癌前病变（OPL）的能力有限，这些病变具有发展为浸润性SCC的高风险，而这些病变具有低风险。我们研究了定量组织表型（QTP）的潜力，通过高分辨率图像分析测量，以确定重度异型增生/原位癌（CIS;已知具有增加的进展风险），并预测在增生或轻度/中度异型增生中进展为癌症。我们生成了一个核表型评分（nuclear phenotype score，简写为nuclear phenotype score），这是五个核形态特征的组合，可以最好地区分4，027个“正常”核（选自29个正常口腔活检）和4，298个“异常”核（选自30个SCC活检）。然后确定了一组69个OPL的这一比值。与增生或轻度/中度不典型增生相比，重度不典型增生/CIS显示出显著增加。然而，在后一组中，高水平的等位基因与高风险杂合性缺失（洛）模式的存在密切相关。增生或轻度/中度异型增生进展为癌症与未进展为癌症之间存在统计学差异。TNPS高的个体进展的相对风险增加了10倍。在多变量考克斯模型中，洛缺失和NIPS是癌症发展的最强预测因子。这些数据表明，QTP可用于识别需要分子评价的病变，并应与此类方法相结合，以便于识别具有高进展风险的增生或轻度/中度异型增生OPL。
The importance of early diagnosis in improving mortality and morbidity rates of oral squamous cell carcinoma (SCC) has long been recognized. However, a major challenge for early diagnosis is our limited ability to differentiate oral premalignant lesions (OPL) at high risk of progressing into invasive SCC from those at low risk. We investigated the potential of quantitative tissue phenotype (QTP), measured by high-resolution image analysis, to identify severe dysplasia/ carcinoma in situ (CIS; known to have an increased risk of progression) and to predict progression to cancer within hyperplasia or mild/moderate dysplasia. We generated a nuclear phenotype score (NPS), a combination of five nuclear morphometric features that best discriminate 4,027 "normal" nuclei (selected from 29 normal oral biopsies) from 4,298 "abnormal" nuclei (selected from 30 SCC biopsies). This NPS was then determined for a set of 69 OPLs. Severe dysplasia/CIS showed a significant increase in NPS compared with hyperplasia or mild/moderate dysplasia. However, within the latter group, elevated NPS was strongly associated with the presence of high-risk loss of heterozygosity (LOH) patterns. There was a statistical difference between NPS of hyperplasia or mild/ moderate dysplasia that progressed to cancer and those that did not. Individuals with a high TNPS had a 10-fold increase in relative risk of progression. In the multivariate Cox model, LOH and NIPS together were the strongest predictors for cancer development. These data suggest that QTP could be used to identify lesions that require molecular evaluation and should be integrated with such approaches to facilitate the identification of hyperplasia or mild/moderate dysplasia OPLs at high risk of progression.