Noutomi Y, Oga A, Uchida K, Okafuji M, Ita M, Kawauchi S, Furuya T, Ueyama Y, Sasaki K
Department of Pathology, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube 755-8505, Yamaguchi, Japan.
J Pathol. 2006 Sep;210(1):67-74. doi: 10.1002/path.2015.
To clarify the genetic pathway(s) involved in the development and progression of oral squamous cell carcinoma (OSCC), as well as the relationship between genetic aberrations and biological characteristics of OSCC tumours, comparative genomic hybridization was used to analyse genetic alterations in both primary OSCCs and adjacent dysplastic lesions of the same biopsy specimens from 35 patients. Gain of 8q22-23 was the most frequent alteration in both OSCC and mild dysplasia, and was considered the earliest event in the process of oral tumourigenesis. The average number of DNA sequence copy number aberrations (DSCNAs) increased with progression from mild dysplasia to invasive carcinoma (r = 0.737, n = 70, p < 0.001). OSCC samples were classified as having a large or small number of DSCNAs (OSCC-L, 21.4 +/- 4.7 DSCNAs or OSCC-S, 10.0 +/- 1.7 DSCNAs, respectively; p < 0.0001). Gains of 3q26-qter, 8q, 11q13, 14q, and 20q and losses of 4q, 5q12-22, 6q, 8p, 13q, and 18q22-qter were common to OSCC-L and OSCC-S. Gains of 5p15, 7p, 17q11-22, and 18p and losses of 3p14-21, 4p, and 9p were detected exclusively in OSCC-L. The average number of DSCNAs depended on whether the samples showed OSCC- L or dysplasia plus OSCC-L, or showed OSCC-S or dysplasia plus OSCC-S (p = 0.001). Gain of 5p15 and losses of 4p and 9p were detected even in dysplastic lesions adjacent to OSCC-L samples. Loss of 4p was associated with node metastasis by multivariate analysis (p = 0.013). OSCC-L tumours were more often T3-T4 stage tumours than T1-T2 stage tumours (p = 0.03). These findings suggest that two different types of OSCC, OSCC-L associated with high-stage cancer and OSCC-S associated with low-stage cancer, arise from different types of dysplasia via different genetic pathways.
为了阐明参与口腔鳞状细胞癌（OSCC）发生和发展的遗传途径，以及OSCC肿瘤的基因畸变与生物学特性之间的关系，采用比较基因组杂交技术分析了35例患者同一活检标本的原发性OSCC及其相邻发育异常病变中的基因改变。8q22 - 23区域的扩增是OSCC和轻度发育异常中最常见的改变，被认为是口腔肿瘤发生过程中的最早事件。DNA序列拷贝数畸变（DSCNAs）的平均数量随着从轻度发育异常到浸润性癌的进展而增加（r = 0.737，n = 70，p < 0.001）。OSCC样本被分为具有大量或少量DSCNAs（分别为OSCC-L，21.4±4.7个DSCNAs或OSCC-S，10.0±1.7个DSCNAs；p < 0.0001）。3q26 - qter、8q、11q13、14q和20q的扩增以及4q、5q12 - 22、6q、8p、13q和18q22 - qter的缺失在OSCC-L和OSCC-S中都很常见。5p15、7p、17q11 - 22和18p的扩增以及3p14 - 21、4p和9p的缺失仅在OSCC-L中检测到。DSCNAs的平均数量取决于样本显示的是OSCC-L还是发育异常加OSCC-L，或者显示的是OSCC-S还是发育异常加OSCC-S（p = 0.001）。即使在与OSCC-L样本相邻的发育异常病变中也检测到了5p15的扩增以及4p和9p的缺失。多因素分析显示4p的缺失与淋巴结转移相关（p = 0.013）。OSCC-L肿瘤比T1 - T2期肿瘤更常为T3 - T4期肿瘤（p = 0.03）。这些发现表明，两种不同类型的OSCC，即与高分期癌症相关的OSCC-L和与低分期癌症相关的OSCC-S，通过不同的遗传途径源自不同类型的发育异常。
