title: Molecular diagnosis of response to neoadjuvant chemoradiation therapy in patients with locally advanced rectal cancer.
abstract: BACKGROUND
  Pathologic complete response (pCR) to neoadjuvant chemoradiation (CRT) is an important prognostic factor in locally advanced rectal cancer. However, it is uncertain if histopathological techniques accurately detect pCR. We tested a novel molecular approach for detecting pCR and compared it with current histopathological approaches.
  
  
  METHODS
  Pretreatment tumor biopsies and surgical specimens were collected from 96 patients with locally advanced rectal cancer treated with neoadjuvant CRT and surgery. Tumor response was categorized by tumor regression grade. Tumor DNA from pre-CRT tumor biopsies was screened for K-ras and p53 mutations. DNA from paired surgical specimens was then screened for the same mutations using highly sensitive polymerase chain reaction-based techniques.
  
  
  RESULTS
  Sixty-eight of 96 (71%) pretreatment biopsies harbored K-ras and/or p53 mutation; 36 (38%) had K-ras mutations, 52 (54%) had p53 mutations, and 20 (21%) carried both mutations. Of 70 patients with tumor regression grades 1 to 3, sixty-six (94%) had a concordant K-ras and p53 mutation profile in pre- and post-treatment tissues. Of 26 patients with tumor regression grade 0 (pCR), 12 had K-ras or p53 mutations in pretreatment biopsies. Of these, 2 (17%) patients had the same K-ras (n = 1) or p53 (n = 1) mutation detected in post-treatment tissue.
  
  
  CONCLUSIONS
  Sensitive molecular techniques detect K-ras and p53 mutations in post-CRT surgical specimens in some patients with a pCR. This suggests histopathological techniques might not be completely accurate, and some patients diagnosed with a pCR to CRT might have occult cancers cells in their surgical specimens.
authors: Department of Surgery, City of Hope, Duarte, CA, USA.
authors: Zhenbin
authors: Z
authors: Chen
authors: Marjun P
authors: MP
authors: Duldulao
authors: Wenyan
authors: W
authors: Li
authors: Wendy
authors: W
authors: Lee
authors: Joseph
authors: J
authors: Kim
authors: Julio
authors: J
authors: Garcia-Aguilar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001706:Biopsy; D017024:Chemotherapy, Adjuvant; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D016158:Genes, p53; D011905:Genes, ras; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D004273:DNA, Neoplasm