Kuwabara S, Ajioka Y, Watanabe H, Hitomi J, Nishikura K, Hatakeyama K
First Department of Pathology, Niigata University School of Medicine.
Jpn J Cancer Res. 1998 Apr;89(4):405-10. doi: 10.1111/j.1349-7006.1998.tb00578.x.
In esophageal squamous cell carcinoma, p53 gene mutations have been analyzed for inter- or intra-patient heterogeneity but only a few studies have investigated intratumoral heterogeneity. We investigated this question within individual esophageal cancers, and also in their lymph-node metastases in 8 cases. Analyzing the p53 gene sequence by direct sequencing of polymerase chain reaction products, we found heterogeneity for p53 mutations in the pre-invasive area in 3 esophageal cancers. In all areas sampled in the invasive portion of each cancer, the p53 mutational status was identical in a given tumor. In heterogeneous tumors, the invasive area showed one of the p53 mutations found in the pre-invasive area. In nodal metastases, the p53 mutation was identical to that in the invasive area of each primary tumor. These data suggest that the timing of p53 alteration is not as early as might have been expected, indicating that, in regard to p53 gene alteration, some esophageal cancers are composed of various subclones in the pre-invasive stage with invasiveness developing in one of them, which becomes predominant through clonal selection.
在食管鳞状细胞癌中，已对p53基因突变进行了患者间或患者内异质性分析，但仅有少数研究调查了肿瘤内异质性。我们在8例个体食管癌及其淋巴结转移灶中研究了这个问题。通过对聚合酶链反应产物进行直接测序来分析p53基因序列，我们发现3例食管癌的浸润前区域存在p53突变的异质性。在每个癌症浸润部分的所有采样区域中，特定肿瘤的p53突变状态是相同的。在异质性肿瘤中，浸润区域显示出在浸润前区域发现的p53突变之一。在淋巴结转移灶中，p53突变与每个原发肿瘤浸润区域的突变相同。这些数据表明，p53改变的时间并不像预期的那么早，这表明，就p53基因改变而言，一些食管癌在浸润前阶段由各种亚克隆组成，其中一个亚克隆发生侵袭性，通过克隆选择成为优势亚克隆。
