title: Chemoresponsiveness associated with canonical molecular changes in colorectal adenocarcinomas.
abstract: BACKGROUND
  The canonical molecular changes in colorectal tumorigenesis were assessed for correlation with response to chemotherapy, in order to identify candidate markers.
  
  
  METHODS
  In total, 156 patients received adjuvant postoperative fluoropyrimidine-based chemotherapy and 32 patients received oxaliplatin- or irinotecan-based chemotherapy following palliative surgery or for metastatic or recurrent colorectal tumors. Representative molecular changes in tumor tissues, including adenomatous polyposis coli (APC) gene, wingless-type MMTV integration site family (Wnt), mismatch repair (MMR), RAF, transforming growth factor (TGF)-beta, bone morphogenetic protein, and p53, had been previously determined, with an additional 42 patients included in this analysis.
  
  
  RESULTS
  The disease-free survival period (mean+/-SEM) was significantly longer after fluoropyrimidine-based adjuvant chemotherapy in tumors with TGF-beta2 expression (42+/-1.4 vs. 21+/-4.7 months; p=0.005) and D18S46 loss of heterozygosity or microsatellite instability (45.7+/-1.5 vs. 40.5+/-1.4 months; p=0.048). In the metastatic settings, the high disease-control rate of oxaliplatin and irinotecan regimens correlated significantly with wild-type APC and intact MMR, respectively, relative to mutant APC and defective MMR (p=0.013, respectively). Interestingly, specific molecular steps of tumorigenensis were closely associated with particular toxicities.
  
  
  CONCLUSIONS
  A subset of molecular changes occurring during colorectal tumorigenesis showed significant associations with therapeutic responses and toxicities to chemotherapy regimens, suggesting that these changes may be candidate predictors of chemoresponsiveness with further validation.
authors: Department of Surgery, University of Ulsan College of Medicine, 388-1 Poongnap-2-Dong Songpa-Ku, Seoul 138-736, Korea. jckim@amc.seoul.kr
authors: Jin C
authors: JC
authors: Kim
authors: Seon A
authors: SA
authors: Roh
authors: Dong H
authors: DH
authors: Cho
authors: Tae W
authors: TW
authors: Kim
authors: Sang N
authors: SN
authors: Yoon
authors: Chan W
authors: CW
authors: Kim
authors: Chang S
authors: CS
authors: Yu
authors: Seon Y
authors: SY
authors: Kim
authors: Yong S
authors: YS
authors: Kim
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000556:secondary; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D053843:DNA Mismatch Repair; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019656:Loss of Heterozygosity; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D010166:Palliative Care; D015996:Survival Rate; D053781:Transforming Growth Factor beta2 / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D048490:raf Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D053781:Transforming Growth Factor beta2; D016159:Tumor Suppressor Protein p53; D051153:Wnt Proteins; D048490:raf Kinases