首页|MUC5AC/β-catenin expression and KRAS gene alteration in laterally spreading colorectal tumors

MUC5AC/β-catenin expression and KRAS gene alteration in laterally spreading colorectal tumors

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To clarify differences in mucin phenotype,proliferative activity and oncogenetic alteration among subtypes of colorectal laterally spreading tumor (LST).METHODS:LSTs,defined as superficial elevated lesions greater than 10 mm in diameter with a low vertical axis,were macroscopically classified into two subtypes:(1) a granular type (Gr-LST) composed of superficially spreading aggregates of nodules forming a flat-based lesion with a granulonodular and uneven surface; and (2) a non-granular type (NGr-LST) with a flat smooth surface and an absence of granulonodular formation.A total of 69 LSTs,comprising 36 Gr-LSTs and 33 NGr-LSTs,were immunohistochemically stained with MUC2,MUC5AC,MUC6,CD10 (markers of gastrointestinal cell lineage),p53,β-catenin and Ki-67 antibodies,and examined for alteration in exon 1 of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and exon 15 of v-raf murine sarcoma viral oncogene homologue B1 (BRAF) by polymerase chain reaction followed by direct sequencing.RESULTS:Histologically,15 Gr-LST samples were adenomas with low-grade dysplasia (LGD),12 were highgrade dysplasia (HGD) and 9 were adenocarcinomas invading the submucosa (INV),while 12 NGr-LSTs demonstrated LGD,14 HGD and 7 INV.In the proximal colon,MUC5AC expression was significantly higher in the Gr-type than the NGr-type.MUC6 was expressed only in NGr-LST.MUC2 or CD10 did not differ,P53 expression demonstrated a significant stepwise increment in progression through LGD-HGD-INV with both types of LST.Nuclear β-catenin expression was significantly higher in the NGr-type.Ki-67 expression was significantly higher in the Gr-type in the lower one third zone of the tumor.In proximal,but not distal colon tumors,the incidence of KRAS provided mutation was significantly higher in the Gr-type harboring a specific mutational pattern (G12V).BRAF mutations (V600E) were detected only in two Gr-LSTs.CONCLUSION:The two subtypes of LST,especially in the proximal colon,have differing phenotypes of gastrointestinal cell lineage,proliferation and activation of Wnt/β-catenin or RAS/RAF/extracellular signalregulated kinase signaling.

Laterally spreading tumorMucin core proteinColonβ-cateninImmunohistochemistryv-Kiras2 Kirsten rat sarcoma viral oncogene homologDirect sequencingAdenoma-carcinoma sequence

Kosaburo Nakae、Hiroyuki Mitomi、Tsuyoshi Saito、Michiko Takahashi、Takashi Morimoto、Yasuhiro Hidaka、Naoto Sakamoto

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Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1Hongo, Bunkyo-ku, Tokyo 113-8421, Japan

Department of Human Pathology, Juntendo University School of Medicine, 1-1-19 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

A grant-in-aid for General Scientific Research from the Ministry of Education,Science,Sports and Culture to Hiroyuki MitomiTsuyoshi Saito

2159039423590434

2012

世界胃肠病学杂志(英文版)
太原消化病研治中心

世界胃肠病学杂志(英文版)

SCI
影响因子:1.001
ISSN:1007-9327
年,卷(期):2012.18(39)
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