Most oral cancers arise from oral potentially malignant lesions, which show varying grades of dysplasia. Risk of progression increases with increasing grade of dysplasia; however, risk prediction among oral low-grade dysplasia (LGD), that is, mild and moderate dysplasia can be challenging as only 5%–15% transform. Moreover, grading of dysplasia is subjective and varies with the area of the lesion being biopsied. To date, no biomarkers or tools are used clinically to triage oral LGDs. This study uses a combination of DNA ploidy and chromatin organization (CO) scores from cells obtained from lesion brushings to identify oral LGDs at high-risk of progression. A total of 130 lesion brushings from patients with oral LGDs were selected of which 16 (12.3%) lesions progressed to severe dysplasia or cancer. DNA ploidy and CO scores were analyzed from nuclear features measured by our in-house DNA image cytometry (DNA-ICM) system and used to classify brushings into low-risk and high-risk. A total of 57 samples were classified as high-risk of which 13 were progressors. High-risk DNA brushing was significant for progression ( P = 0.001) and grade of dysplasia ( P = 0.004). Multivariate analysis showed high-risk DNA brushing showed 5.1- to 8-fold increased risk of progression, a stronger predictor than dysplasia grading and lesion clinical features. DNA-ICM can serve as a non-invasive, high-throughput tool to identify high-risk lesions several years before transformation. This will help clinicians focus on such lesions whereas low-risk lesions may be spared from unnecessary biopsies. Prevention Relevance: DNA ploidy and chromatin organization of cells collected from oral potentially malignant lesions (OPMLs) can identify lesions at high-risk of progression several years prior. This non-invasive test would enable clinicians to triage high-risk (OPMLs) for closer follow-up while low-risk lesions can undergo less frequent biopsies reducing burden on healthcare resources.

中文翻译：

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使用基于刷牙的 DNA 倍性和染色质组织分析预测低度口腔发育不良的进展

大多数口腔癌起源于口腔潜在的恶性病变，这些病变表现出不同程度的发育不良。进展风险随着异型增生程度的增加而增加；然而，口腔低度不典型增生（LGD）（即轻度和中度不典型增生）的风险预测可能具有挑战性，因为只有 5%–15% 的转化率。此外，不典型增生的分级是主观的，并且随着活检病变的区域而变化。迄今为止，临床上还没有生物标志物或工具用于对口服 LGD 进行分类。本研究使用从病变刷牙中获得的细胞的 DNA 倍性和染色质组织 (CO) 评分的组合来识别具有高进展风险的口腔 LGD。共选择了 130 例口腔 LGD 患者的病灶刷牙，其中 16 例 (12.3%) 病灶进展为严重的不典型增生或癌症。DNA 倍性和 CO 评分通过我们的内部 DNA 图像细胞仪 (DNA-ICM) 系统测量的核特征进行分析，并用于将刷牙分为低风险和高风险。共有 57 个样本被归类为高危样本，其中 13 个为进展者。高风险 DNA 刷牙对进展（ P = 0.001）和发育不良等级（ P = 0.004）具有显着意义。多变量分析显示，高风险 DNA 刷牙显示进展风险增加 5.1 至 8 倍，这是比发育不良分级和病变临床特征更强的预测因子。DNA-ICM 可以作为一种非侵入性、高通量工具，在转化前几年识别高风险病变。这将有助于临床医生专注于此类病变，而低风险病变可能免于不必要的活检。预防相关：从口腔潜在恶性病变 (OPML) 收集的细胞的 DNA 倍性和染色质组织可以识别几年前处于高风险进展的病变。这种非侵入性测试将使临床医生能够对高风险 (OPML) 进行分类以进行更密切的随访，而低风险病变可以进行较少频率的活检，从而减轻医疗资源的负担。