More than 1.9 million new colorectal cancer(CRC)cases and 935000 deaths were estimated to occur worldwide in 2020,representing about one in ten cancer cases and deaths.Overall,colorectal ranks third in incidence,but s...More than 1.9 million new colorectal cancer(CRC)cases and 935000 deaths were estimated to occur worldwide in 2020,representing about one in ten cancer cases and deaths.Overall,colorectal ranks third in incidence,but second in mortality.More than half of the patients are in advanced stages at diagnosis.Treatment options are complex because of the heterogeneity of the patient population,including different molecular subtypes.Treatments have included conventional fluorouracil-based chemotherapy,targeted therapy,immunotherapy,etc.In recent years,with the development of genetic testing technology,more and more targeted drugs have been applied to the treatment of CRC,which has further prolonged the survival of metastatic CRC patients.展开更多
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 le...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 subtypes of LST, especially in the proximal colon, have differing phenotypes of gastrointestinal cell lineage, proliferation and activa- tion of Wnt/β-catenin or RAS/RAF/extracellular signal- regulated kinase signaling.展开更多
目的探讨胃癌的临床病理特征与鼠类肉瘤病毒癌基因(kirsten rat sarcoma viral oncogene,KRAS)突变的相关性。方法选择120例胃癌患者(胃癌组)与120例胃良性病变患者(良性组),提取2组患者病理组织的DNA,对KRAS基因第2号外显子进行扩增,记...目的探讨胃癌的临床病理特征与鼠类肉瘤病毒癌基因(kirsten rat sarcoma viral oncogene,KRAS)突变的相关性。方法选择120例胃癌患者(胃癌组)与120例胃良性病变患者(良性组),提取2组患者病理组织的DNA,对KRAS基因第2号外显子进行扩增,记录KRAS基因突变情况并进行相关性分析。结果胃癌组的KRAS基因突变率为75.0%,显著高于良性组的15.0%(P<0.05)。在120例胃癌患者中,不同临床分期、淋巴结转移、分化程度、远处转移、浸润深度患者的KRAS基因突变率对比,差异有统计学意义(P<0.05)。胃癌组患者随访至今,平均随访时间为(15.22±2.48)月,死亡12例,死亡率为10.0%。单因素和多因素Cox回归分析显示KRAS基因突变率、临床分期、淋巴结转移、分化程度、远处转移、浸润深度都为影响胃癌患者预后的危险因素(P<0.05)。结论KRAS基因突变在胃癌组织中比较常见,与患者的临床病理特征显著相关,可以作为预测胃癌发生和预后的潜在生物标志物。展开更多
文摘More than 1.9 million new colorectal cancer(CRC)cases and 935000 deaths were estimated to occur worldwide in 2020,representing about one in ten cancer cases and deaths.Overall,colorectal ranks third in incidence,but second in mortality.More than half of the patients are in advanced stages at diagnosis.Treatment options are complex because of the heterogeneity of the patient population,including different molecular subtypes.Treatments have included conventional fluorouracil-based chemotherapy,targeted therapy,immunotherapy,etc.In recent years,with the development of genetic testing technology,more and more targeted drugs have been applied to the treatment of CRC,which has further prolonged the survival of metastatic CRC patients.
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. 21590394to Tsuyoshi Saito, No. 23590434, To-kyo, Japan
文摘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 subtypes of LST, especially in the proximal colon, have differing phenotypes of gastrointestinal cell lineage, proliferation and activa- tion of Wnt/β-catenin or RAS/RAF/extracellular signal- regulated kinase signaling.
文摘目的探讨胃癌的临床病理特征与鼠类肉瘤病毒癌基因(kirsten rat sarcoma viral oncogene,KRAS)突变的相关性。方法选择120例胃癌患者(胃癌组)与120例胃良性病变患者(良性组),提取2组患者病理组织的DNA,对KRAS基因第2号外显子进行扩增,记录KRAS基因突变情况并进行相关性分析。结果胃癌组的KRAS基因突变率为75.0%,显著高于良性组的15.0%(P<0.05)。在120例胃癌患者中,不同临床分期、淋巴结转移、分化程度、远处转移、浸润深度患者的KRAS基因突变率对比,差异有统计学意义(P<0.05)。胃癌组患者随访至今,平均随访时间为(15.22±2.48)月,死亡12例,死亡率为10.0%。单因素和多因素Cox回归分析显示KRAS基因突变率、临床分期、淋巴结转移、分化程度、远处转移、浸润深度都为影响胃癌患者预后的危险因素(P<0.05)。结论KRAS基因突变在胃癌组织中比较常见,与患者的临床病理特征显著相关,可以作为预测胃癌发生和预后的潜在生物标志物。
