Department of Molecular and Cellular Pathology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
Pathol Int. 2010 Jun;60(6):466-71. doi: 10.1111/j.1440-1827.2010.02545.x.
We examined 11 cases of carcinoma arising from Barrett's esophagus consisting of two adenocarcinomas in situ (ACIS), two intramucosal adenocarcinomas, and seven overt invasive adenocarcinomas. Overexpression of p53 (implying a mutation of the p53 gene), ERBB2, and EGFR was measured by immunohistochemistry, and gene amplification of ERBB2 and EGFR was measured by fluorescence in situ hybridization (FISH). In all cases of ACIS and the intramucosal adenocarcinomas, almost all cancer cells overexpressed p53, however the populations overexpressing ERBB2 and EGFR varied in different cases: in one ACIS, ERBB2 was coexpressed in all the cancer cells, in the other ACIS and one intramucosal adenocarcinoma, ERBB2 was overexpressed in about 50% and only 10% of the p53-positive cells respectively. EGFR was co-expressed in 20% in the other intramucosal adenocarcinoma. Protein overexpression of ERBB2 or EGFR corresponded to the amplification of their respective genes on a cell by cell basis. These gene amplifications, however, were not found in the seven invasive adenocarcinomas. Thus we speculate that the gene amplification occurred late in the dysplasia-carcinoma sequence probably after the mutation of p53. Furthermore, new clonal expansion accompanied by tumor invasion might have extinguished the originally amplified genes in these tumors.
我们检查了 11 例巴雷特食管癌病例，包括 2 例原位腺癌 (ACIS)、2 例黏膜内腺癌和 7 例明显浸润性腺癌。通过免疫组织化学检测 p53（提示 p53 基因突变）、ERBB2 和 EGFR 的过表达，通过荧光原位杂交 (FISH) 检测 ERBB2 和 EGFR 的基因扩增。在所有 ACIS 和黏膜内腺癌病例中，几乎所有癌细胞都过表达了 p53，但不同病例中过表达 ERBB2 和 EGFR 的细胞群有所不同：在一个 ACIS 中，所有癌细胞都共表达 ERBB2，在另一个 ACIS 和一个黏膜内腺癌中，ERBB2 分别在约 50%和 10%的 p53 阳性细胞中过表达。另一个黏膜内腺癌中 EGFR 共表达 20%。ERBB2 或 EGFR 的蛋白过表达与相应基因在细胞水平上的扩增相对应。然而，这些基因扩增在 7 例浸润性腺癌中未发现。因此，我们推测基因扩增发生在异型增生-癌序列的晚期，可能在 p53 突变之后。此外，新的克隆扩展伴随着肿瘤侵袭，可能已经使这些肿瘤中最初扩增的基因失活。
