PURPOSE:This study was designed to investigate whether the histologic types of the primary lesion and of metastatic lymph nodes in Stage III colon cancer are useful as prognostic factors.The usefulness of adjuvant che...PURPOSE:This study was designed to investigate whether the histologic types of the primary lesion and of metastatic lymph nodes in Stage III colon cancer are useful as prognostic factors.The usefulness of adjuvant chemotherapy in a randomized,controlled trial by using these prognostic factors as stratification criteria was also investigated.METHODS:Stage III colon cancer patients were enrolled and were divided into two groups:Group W,in which the histologic type of both primary tumors and metastatic lymph nodes was well-differentiated adenocarcinoma;and Group U,in which the primary tumors and the metastatic lymph nodes were of any type other than well-differentiated.Group W patients were assigned to Treatment Arm A(surgery alone) or Arm B(surgery,then 1-hexylcarbamoyl-5-fluorouracil) ;and Group U patients,to Treatment Arm C(same as B) ,and Arm D(surgery + 1-hexylcar-bamoyl-5-fluorouracil + mitomycin C) .RESULTS:The Group W five-year survival rate was significantly superior to that in Group U(P = 0.0035) .There was a better survival rate in Treatment Arm A than Arm B(P = 0.0321) ,but no difference between Treatment Arms C and D.CONCLUSIONS:In Stage III colon cancer,the prognosis of cases whose primary lesion and lymph node tissues are both well differentiated is extremely good.In such cases,it is possible for adjuvant chemotherapy to have a deleterious effect,and therefore,it is not recommended.展开更多
PURPOSE:Role and timing of frameshift mutations during carcinogenesis in hereditary nonpolyposis colorectal cancer have not been examined.This study was designed to clarify the relationship between frameshift mutation...PURPOSE:Role and timing of frameshift mutations during carcinogenesis in hereditary nonpolyposis colorectal cancer have not been examined.This study was designed to clarify the relationship between frameshift mutations and clinicopathologic features in colorectal cancer from patients with hereditary nonpolyposis colorectal cancer.METHODS:Thirty-one colorectal cancers from patients with hereditary nonpolyposis colorectal cancer at different clinicopathologic stages were analyzed for frameshift mutation in 18 genes.RESULTS:The frameshift mutations of the ACVR2 and PTHLH genes were found to have an extremely high frequency(94-100 percent)in all pathologic stages,and mutation of the MARCKS gene also was high(94 percent)in Dukes B and C cancers.These frequencies were higher than the frequency of TGF βRII gene inactivation(64-88 percent).Mutations of the hMSH3,TCF4,CASP5,RIZ,RAD50,and MBD4 genes were comparatively frequent(>35 percent)in all stages.Frequencies of inactivation of the MARCKS,BAX,IGF IIR,and PTEN genes were significantly higher in Dukes B and C cancers than in Dukes A cancer(P < 0.05).The number of accumulated frameshift mutations was larger in Dukes B and C cancers(9.4)than in Dukes A cancer(6.8)(P = 0.003).CONCLUSIONS:The present data suggest that the disruption of the transforming growth factor-βsuperfamily signaling pathway by the alteration of the ACVR2 and/or TGFβRII genes and the disruption of antiproliferative function by the PTHLH gene alteration contribute to the development of early colorectal cancer.Moreover,the further accumulation of alterations in the MARCKS,BAX,IGF IIR,and PTEN genes seem to be associated with progression from early to advanced colorectal cancer from patients with hereditary nonpolyposis colorectal cancer.展开更多
文摘PURPOSE:This study was designed to investigate whether the histologic types of the primary lesion and of metastatic lymph nodes in Stage III colon cancer are useful as prognostic factors.The usefulness of adjuvant chemotherapy in a randomized,controlled trial by using these prognostic factors as stratification criteria was also investigated.METHODS:Stage III colon cancer patients were enrolled and were divided into two groups:Group W,in which the histologic type of both primary tumors and metastatic lymph nodes was well-differentiated adenocarcinoma;and Group U,in which the primary tumors and the metastatic lymph nodes were of any type other than well-differentiated.Group W patients were assigned to Treatment Arm A(surgery alone) or Arm B(surgery,then 1-hexylcarbamoyl-5-fluorouracil) ;and Group U patients,to Treatment Arm C(same as B) ,and Arm D(surgery + 1-hexylcar-bamoyl-5-fluorouracil + mitomycin C) .RESULTS:The Group W five-year survival rate was significantly superior to that in Group U(P = 0.0035) .There was a better survival rate in Treatment Arm A than Arm B(P = 0.0321) ,but no difference between Treatment Arms C and D.CONCLUSIONS:In Stage III colon cancer,the prognosis of cases whose primary lesion and lymph node tissues are both well differentiated is extremely good.In such cases,it is possible for adjuvant chemotherapy to have a deleterious effect,and therefore,it is not recommended.
文摘PURPOSE:Role and timing of frameshift mutations during carcinogenesis in hereditary nonpolyposis colorectal cancer have not been examined.This study was designed to clarify the relationship between frameshift mutations and clinicopathologic features in colorectal cancer from patients with hereditary nonpolyposis colorectal cancer.METHODS:Thirty-one colorectal cancers from patients with hereditary nonpolyposis colorectal cancer at different clinicopathologic stages were analyzed for frameshift mutation in 18 genes.RESULTS:The frameshift mutations of the ACVR2 and PTHLH genes were found to have an extremely high frequency(94-100 percent)in all pathologic stages,and mutation of the MARCKS gene also was high(94 percent)in Dukes B and C cancers.These frequencies were higher than the frequency of TGF βRII gene inactivation(64-88 percent).Mutations of the hMSH3,TCF4,CASP5,RIZ,RAD50,and MBD4 genes were comparatively frequent(>35 percent)in all stages.Frequencies of inactivation of the MARCKS,BAX,IGF IIR,and PTEN genes were significantly higher in Dukes B and C cancers than in Dukes A cancer(P < 0.05).The number of accumulated frameshift mutations was larger in Dukes B and C cancers(9.4)than in Dukes A cancer(6.8)(P = 0.003).CONCLUSIONS:The present data suggest that the disruption of the transforming growth factor-βsuperfamily signaling pathway by the alteration of the ACVR2 and/or TGFβRII genes and the disruption of antiproliferative function by the PTHLH gene alteration contribute to the development of early colorectal cancer.Moreover,the further accumulation of alterations in the MARCKS,BAX,IGF IIR,and PTEN genes seem to be associated with progression from early to advanced colorectal cancer from patients with hereditary nonpolyposis colorectal cancer.
