Molecular biological analysis of oral multiple tumor and multiple precancer

口腔多发性肿瘤及多发性癌前病变的分子生物学分析

• 批准号: 13672072
• 负责人: SATOH Akira
• 金额: $ 1.47万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672072/
• 关键词: multiple primary tumors; oral cancer; precancer; loss of heterozygosity; microsatellite alterations; 二次癌; 口腔扁平上皮癌; 前癌病変; field cancerization theory

Multiple primary tumors in patients with head and neck squamous cell carcinoma has become an increasingly important factor in clinical treatment decision. Currently, clinical and histologic parameters are used to determine whether or not multiple primary tumor is present Recent studies suggest that many multiple primary tumors in the upper aerodigestive tract have a common clonal origin, challenging the longstanding multiclonal origin concept. To determine genetic relationships among multiple oral cancerous and precancerous lesions, we analysed 100 lesions from 26 Japanese patients. Lesion development was synchronous and metachronous. We looked for patterns of microsatellite alterations using seven markers at chromosomes 3pl4, 9p21, and 17pl3, where microsatellite alteration occurs early in oral carcinogenesis. Loss of heterozygosity was found in 52.6%(41/78), 62.53% (60/96), and 59.3% (32/54) of informative multiple oral cancerous and precancerous lesions at 3p14, 9p21, and 17p13, respectively. Microsatellite instability was observed in 11, 26 and 13% of the samples at 3p14, 9p21, and 17pl3 markers, respectively. Patterns of microsatellite alterations were concordant in only nine (14%) of 63 lesions from four (18%) of 22 patients who initially presented with noninvasive lesions. However, two of four patients with invasive cancer as indexed lesion showed 16 (43%) clonally related multiple oral cancerous and precancerous lesions among 37 lesions (P=0.003). The results suggest that the majority of multiple oral cancerous and precancerous lesions arise from clonally independent cells affected by field cancerization. However, the probability of mucosal spread of clonal malignant or premalignant cells may increase along with malignant progression.

头颈部鳞状细胞癌患者的多原发肿瘤已成为临床治疗决策中越来越重要的因素。目前，临床和组织学参数用于确定是否存在多原发性肿瘤。最近的研究表明，许多上呼吸消化道多原发性肿瘤具有共同的克隆起源，挑战了长期存在的多克隆起源概念。为了确定多个口腔癌和癌前病变之间的遗传关系，我们分析了26名日本患者的100个病变。病变的发展是同步和异时的。我们使用染色体3 p14、9 p21和17 p13上的7个标记寻找微卫星改变的模式，其中微卫星改变发生在口腔癌发生的早期。在口腔多发癌和癌前病变中，3 p14、9 p21和17 p13位点的杂合性丢失率分别为52.6%（41/78）、62.53%（60/96）和59.3%（32/54）。在3 p14、9 p21和17 p13标记处分别在11%、26%和13%的样品中观察到微卫星不稳定性。22例患者中有4例（18%）最初表现为非侵袭性病变，63个病变中只有9个（14%）的微卫星改变模式一致。然而，2/4例浸润性癌作为指标病变显示16（43%）克隆相关的口腔多发性癌和癌前病变中的37个病变（P=0.003）。结果表明，大多数口腔多发性癌和癌前病变来自受现场癌变影响的克隆独立细胞。然而，克隆性恶性或癌前细胞的粘膜扩散的可能性可能随着恶性进展而沿着增加。