Clinicopathological studies of cancers of the ampulla of Vater according to the adenomatous components : Evaluation of p53 and PCNA expression in the carcinogenesis of the ampulla of Vater

摘要

近年, 十二指腸乳頭部癌の発癌過程における adenoma-carcinoma sequence の関与が推測され, 前癌病変としての腺腫の重要性が指摘されているが, 種々の分子生物学的因子の adenoma-carcinoma sequence における意義は未だ不明な点が多い。今回我々は十二指腸乳頭部癌の腺腫成分の有無に注目し, 臨床病理学的因子および, p53と proliferating cell nuclear antigen (PCNA) 蛋白発現からみた腺腫成分の意義を考察した。臨床病理学的には低分化型腺癌で腺腫成分を認めなかった以外には, 年齢, 性別, 予後, 腫瘍径, 膵浸潤, 十二指腸浸潤, リンパ節転移で腺腫の有無により有意差を認めなかった。腺腫の有無によるp53異常蛋白発現率には有意差が認められなかったが, 同一症例内での癌部分と腺腫部分の比較において, 癌部分でのp53異常蛋白発現は14.3%に diffuse に, 28.6%に focal に認められ, 腺腫部分では7.1%に diffuse に, 14.3%に focal に認められ, 正常粘膜では全く認められなかった。同一症例内の癌部分のPCNA labeling index (LI) は腺腫部分および正常粘膜に比べ有意に高く, 腺腫部分のPCNALIは正常粘膜とほぼ同じ値を示した。以上から乳頭部癌において adenoma-carcinoma sequence が分化型腺癌の発癌に重要で, p53とPCNAは乳頭部癌における癌と腺腫との組織学的鑑別診断に有用と考えられ, その臨床応用が期待された。 / Since adenoma-carcinoma sequence is thought to be associated with carcinogenesis of the ampulla of Vater, adenomas of the ampulla of Vater are important as precancerous lesions, but few reports of molecular biological studies in carcinomas of the ampilla of Vater exist. We examined the clinicopathological features and expression of p53 and PCNA protein in carcinomas of the ampulla of Vater according to the adenomatous components. On clinicopathological findings, there were more cases of poorly differentiated adenocarcinomas in the group without adenomatous lesion than the group with adenomatous lesion, but other clinicopathological findings (age, sex, prognosis, tumor size, pancreatic invasion, duodenum invasion, lymph node metastasis) were not significantly associated with or without adenomatous components. Diffuse p53 overexpression was observed in 14.3% and focal in 28.6% of cancer compobebt, diffuse in 7.1% and fpcal in 14.3% of adenomatous component, and no p53 overexpression in normal epithelium. The PCNA labeling index (LI) of cancer component was significantly higher than that of adenomatous component or of normal epithelium. Adenomatous components and normal epithelium have almost the same PCNA LI. The results suggest that adenoma carcinoma sequence was important in carcinogenesis of differentiated type adenocarcinomas of the ampulla of Vater and immunohistochemical staining of p53 and OCNA are useful as an adjunct to the histological differential diagnosis between cancer and adenoma.