ヒト肺線癌の特性の分子病理学的解析

1989 Fiscal Year Annual Research Report

• Project/Area Number: 01010082
• Research Institution: National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East
• Principal Investigator: 下里 幸雄 国立がんセンター, 病理部, 部長 (10076979)
• Co-Investigator(Kenkyū-buntansha): 渡辺 慶一 東海大学, 医学部・病理学, 教授 (00055865) ; 関口 清俊 藤田学園保健衛生大学, 医学部・生化学教室, 講師 (50187845) ; 浜田 新七 滋賀医科大学, 第一病理学, 助手 (00172974) ; 桜井 雅温 埼玉県立がんセンター, 病院化学寮法部, 部長 (20025604) ; 横田 淳 国立がんセンター, がん転移研究室, 室長 (10191503)
• Keywords: ヒトの肺 / 線癌 / 染色体異常 / 遺伝子異常 / 核DNAプロイディー / 基質糖蛋白 / 細胞接着分子

Research Abstract

肺小細胞癌でほぼ全例にみられた第3,13,17染色体の部分欠失を肺線癌で検討した結果,それぞれにつき原発巣では60ー100%に,脳転移では80ー100%に欠失を認めた。この所見は癌の発生あるいは悪性度増強には,組織型を問わず同じ遺伝子が関与していることを強く示唆している。
特に3p(-)は原発巣で全例に,かつ比較的早期にみられるので3pに癌抑制遺伝子があることが予想される。非小細胞癌75例につき染色体の核型分析をしたが,染色体数81以上の8症例はすべて線癌で,かつ3p(-)は扁平上皮癌により頻度が高かったことを除き,線癌・扁平上皮癌の二組織型間に差異を見いだすことができなかった。
DNA ploidy,mosaic ploidyの程度の予後との関連をT1NOMO25例とT1N2 29例についてみると,T1N2群でaneuploidyの頻度(p<0.01),mosaic ploidyの頻度(p<0.01),ならびに分裂指数(p<0.05)が有意に高く,肺線癌個々の管理方針の決定に核DNA定量が有効であると考えられた。また,原発巣,リンバ節転移,脳・肝転移についてみると,原発巣と胸郭内リンパ節転移との間に平均DNA量につき差を認めなかったが,脳転移巣,肝転移巣では,原発巣に比べて平均DNA量の大きな症例の頻度が有意に高かった。この所見は,原発巣玉で平均DNA量のより大きなsubcloneが出現し,これが血行転移成立に重要な役割を演じていることを示唆している。
フィブロネクチン(FN)mRNAのED-B可変域におけるスプライシングパターンを検討し,正常肺に比べ,線癌のみならず他の組織型の肺癌においてもED-B+mRNAの増加が確認された。肺癌組織におけるED-B+mRNAの増加は,ED-Bペプチドについての免疫組織学的な検討でも確認された。さらに,FN以下の基質糖蛋白も癌性変化を受けるか否かにつき検討したが,FNほど顕著な癌胎児性調節を受けるものは発見されなかった。

Research Products

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• [Publications] 桜井雅温: "肺癌の染色体異常とoncogene" 呼吸. 8. 1320-1324 (1989)
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• [Publications] Shimosato,Y.: "Basic and Clinical Concepts of Lung Cancer" Kluwer Academic Publishers,Boston, 71-87 (1989)