Molecular biological analysis of oral multiple tumor and multiple precancer

点击翻译按钮获取中文摘要

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.