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

作　　者：Kosaburo Nakae Hiroyuki Mitomi Tsuyoshi Saito Michiko Takahashi Takashi Morimoto Yasuhiro Hidaka Naoto Sakamoto Takashi Yao Sumio Watanabe 

机构地区：[1]Department of Gas-troenterology,Juntendo University School of Medicine,2-1-1 Hongo,Bunkyo-ku,Tokyo 113-8421,Japan [2]Department of Human Pathology,Juntendo University School of Medicine,1-1-19 Hongo,Bunkyo-ku,Tokyo 113-0033,Japan

出　　处：《World Journal of Gastroenterology》2012年第39期5551-5559,共9页世界胃肠病学杂志（英文版）

基　　金：Supported by A grant-in-aid for General Scientific Research from the Ministry of Education, Science, Sports and Culture to Hiroyuki Mitomi, No. 21590394;to Tsuyoshi Saito, No. 23590434, To-kyo, Japan

摘　　要：AIM： To clarify differences in mucin phenotype, prolif- erative activity and oncogenetic alteration among sub- types 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 spread- ing aggregates of nodules forming a fiat-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, 13-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 poly- merase chain reaction followed by direct sequencing. RESULTS： Histologically, 15 Gr-LST samples were ad- enomas with low-grade dysplasia （LGD）, 12 were high- grade 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 ex- pression 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 signifi- cantly 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 signifi- cantly higher in the Gr-type harboring a specific muta- tional pattern （G12V）. BRAF mutations （V600E） were detected only in two Gr-LSTs. CONCLUSION： The two sAIM:To clarify differences in mucin phenotype, prolif-erative 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 poly-merase chain reaction followed by direct sequencing. RESULTS:Histologically, 15 Gr-LST samples were adenomas with low-grade dysplasia (LGD), 12 were high-grade 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 signifi-cantly 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 signifi-cantly 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 gast

关 键 词：Laterally spreading tumor Mucin core pro-tein Colon Β-CATENIN Immunohistochemistry v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog Directsequencing Adenoma-carcinoma sequence 

分 类 号：R735.34[医药卫生—肿瘤]