title: Molecular genetic changes associated with colorectal carcinogenesis are not prognostic for tumor regression following preoperative chemoradiation of rectal carcinoma.
abstract: OBJECTIVE
  Preoperative chemotherapy and radiation has become the standard of care for many patients with rectal cancer. The therapy may have toxicity and delays definitive surgery. It would therefore be desirable to identify those cancers that will not regress with preoperative therapy. We assessed a series of rectal cancers for the molecular changes of loss of heterozygosity of the APC and DCC genes, K-ras mutations, and microsatellite instability, changes that have clearly been associated with rectal carcinogenesis.
  
  
  METHODS
  Diagnostic colonoscopic biopsies from 53 patients who received preoperative chemotherapy and radiation were assayed using polymerase chain reaction techniques followed by single-stranded conformation polymorphism and DNA sequencing. Regression of the primary tumor was evaluated using the surgically removed specimen.
  
  
  RESULTS
  Twenty-three lesions (45%) were found to have a high degree of regression. None of the molecular changes were useful as indicators of regression.
  
  
  CONCLUSIONS
  Recognized molecular changes critical for rectal carcinogenesis including APC and DCC loss of heterozygosity, K-ras mutations, and microsatellite instability are not useful as indicators of tumor regression following chemoradiation for rectal carcinoma.
authors.affiliation: Department of Medicine, Saint Barnabas Medical Center, Livingston, NJ, USA. pzauber@gmail.com
authors.forename: N Peter
authors.initials: NP
authors.lastname: Zauber
authors.forename: Steven P
authors.initials: SP
authors.lastname: Marotta
authors.forename: Errol
authors.initials: E
authors.lastname: Berman
authors.forename: Alison
authors.initials: A
authors.lastname: Grann
authors.forename: Maithili
authors.initials: M
authors.lastname: Rao
authors.forename: Naga
authors.initials: N
authors.lastname: Komati
authors.forename: Kezia
authors.initials: K
authors.lastname: Ribiero
authors.forename: D Timothy
authors.initials: DT
authors.lastname: Bishop
mesh_terms: D000368:Aged; D001706:Biopsy; D015179:Colorectal Neoplasms / Q000235:genetics*; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D017491:Genes, APC; D016163:Genes, DCC / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D053842:Microsatellite Instability; D018807:Polymorphism, Single-Stranded Conformational; D011300:Preoperative Care; D011379:Prognosis; D011446:Prospective Studies; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D012007:Rectum / Q000473:pathology; D012074:Remission Induction / Q000379:methods