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Stomach and Intestine(Tokyo) Volume 45, Issue 6 （May 2010）

胃と腸 45巻6号（2010年5月発行）

Japanese English

今月の主題側方発育型大腸腫瘍（laterally spreading tumor ; LST）─分類と意義

主題

側方発育型大腸腫瘍の臨床病理学的および分子病理学的解析 Analyses of Clinicopathological Findings and Molecular Alterations in Colorectal Laterally Spreading Tumors 菅井有 ¹ , 山野泰穂 ² , 高木亮 ^2,4 , 吉川健二郎 ² , 山本英一郎 ³ , 豊田実 ³ , 塩井義裕 ¹ , 上杉憲幸 ¹ , 千葉俊美 ⁴ , 鈴木一幸 ⁴ Tamotsu Sugai ¹ , Hiroo Yamano ² , Ryou Takagi ^2,4 , Kenjiro Yoshikawa ² , Eiichiro Yamamoto ³ , Minoru Toyota ³ , Yoshihiro Shioi ¹ , Noriyuki Uesugi ¹ , Toshimi Chiba ⁴ , Kazuyuki Suzuki ⁴ ¹岩手医科大学医学部病理学講座分子診断病理学分野 ²秋田赤十字病院消化器病センター ³札幌医科大学医学部生化学講座 ⁴岩手医科大学医学部内科学講座消化器肝臓内科分野 ¹Division of Molecular Diagnostic Pathology, Department of Pathology, School of Medicine, Iwate Medical University, Morioka, Japan ²Division of Gastroenterology, Akita Red Cross Hospital, Akita, Japan ³Department of Biochemistry, Sapporo Medical University, Sapporo, Japan ⁴Division of Gastroenterology, Department of Internal Medicine School of Medicine, Iwate Medical University, Morioka, Japan キーワード： LST , Ki-ras , APC , CIMP , 腺腫内癌 Keyword: LST , Ki-ras , APC , CIMP , 腺腫内癌 pp.939-952

発行日 2010年5月25日 Published Date 2010/5/25

DOI https://doi.org/10.11477/mf.1403101952

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要旨　側方発育型大腸腫瘍（laterally spreading tumor ; LST）の臨床病理学的および分子病理学的解析を行った．最初に，LSTについて臨床病理学的検討を行った（LST-GおよびLST-NGに分類し，さらに前者をLST-GHとLST-GMに，後者をLST-NG-FとLST-NG-PDに亜分類した）．発生部位は，LST-NGにおいて右側大腸に好発し，担癌率はLST-GMとLST-NG-PDで高かった．次に，LST型腺腫において分子病理学的解析を行った．解析方法はPCR-LOH法を用い，LOHとMSIの有無を検討した．PCR-SSCP法および直接シークエンス法で，ki-ras，APC，p53，BRAFの各遺伝子の変異についても解析を行った，最後にCOBRA法で，癌関連遺伝子のメチル化について検討した．分子病理学的にもLST-GとLST-NGは異なっていた．LST-GとLST-NGは臨床病理学的にも分子病理学的にも互いに異なる腫瘍であることが示唆された．

　Colorectal laterally spreading tumors（LST）are classified into LST-G and LST-NG. Previous studies have shown that colorectal LSTs have distinct clinicopathological features and a high malignancy potential. The aims of this study were to analyze the clinicopathological features and molecular findings of colorectal LSTs. A total of 423 LSTs were examined including 252 LST-G and 171 LST-NG types with a view to identifying their clinicopathological features. In addition, molecular study in 64 LSTs that were histlogically diagnosed as adenoma（30 LST-Gs and 34 LST-NGs）was designed for evaluating distinct molecular features using a crypt isolation method. These tumors were examined using PCR-based microsatellite assays, single-strand conformational polymorphism assays and COBRA to detect chromosomal allelic loss, APC, ki-ras, BRAF and p53 gene mutations, and the methylation status at the MLH-1, MGMT, p16, HPP-1, RASSF2A, SFRP1, DKK-1, ZFP64 and SALL4 genes. MSI was also examined. There was significant difference in the tumor location（left/right colon）and histological type between LST-Gs and LST-NGs. On the other hand, the frequency of submucosal cancer was high in some specific types of LSTs. Whereas high frequency of ki-ras and APC mutations, as well as the methylation of ZFP-64, RASSF2A and HPP-1 genes characterized the LST-G type, distinct molecular features were found in LST-NGs. 5q LOH, methylation of the SFRP1 and SALL4 genes were common molecular events in both LST-Gs and LST-NGs. None of MST was detected in the LSTs. The molecular and clinicopathological findings suggest that LST-Gs and LST-NGs have different colorectal tumorigenesis.