title: Detection of tumor DNA at the margins of colorectal cancer liver metastasis.
abstract: OBJECTIVE
  Defining an adequate resection margin of colorectal cancer liver metastases is essential for optimizing surgical technique. We have attempted to evaluate the resection margin through a combination of histopathologic and genetic analyses.
  
  
  METHODS
  We evaluated 88 samples of tumor margins from 12 patients with metastatic colon cancer who each underwent partial hepatectomy of one to six liver metastases. Punch biopsies of surrounding liver tissue were obtained at 4, 8, 12, and 16 mm from the tumor border. DNA from these biopsies was analyzed by a sensitive PCR-based technique, called BEAMing, for mutations of KRAS, PIK3CA, APC, or TP53 identified in the corresponding tumor.
  
  
  RESULTS
  Mutations were identified in each patient's resected tumor and used to analyze the 88 samples circumscribing the tumor-normal border. Tumor-specific mutant DNA was detectable in surrounding liver tissue in 5 of these 88 samples, all within 4 mm of the tumor border. Biopsies that were 8, 12, and 16 mm from the macroscopic visible margin were devoid of detectable mutant tumor DNA and of microscopically visible cancer cells. Tumors with a significant radiologic response to chemotherapy were not associated with any increase in mutant tumor DNA in beyond 4 mm of the main tumor.
  
  
  CONCLUSIONS
  Mutant tumor-specific DNA can be detected beyond the visible tumor margin, but never beyond 4 mm, even in patients whose tumors were larger prior to chemotherapy. These data provide a rational basis for determining the extent of surgical excision required in patients undergoing resection of liver metastases.
authors.affiliation: Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Holdhoff
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schmidt
authors.forename: Frank
authors.initials: F
authors.lastname: Diehl
authors.forename: Nishant
authors.initials: N
authors.lastname: Aggrawal
authors.forename: Philipp
authors.initials: P
authors.lastname: Angenendt
authors.forename: Katharine
authors.initials: K
authors.lastname: Romans
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Edelstein
authors.forename: Michael
authors.initials: M
authors.lastname: Torbenson
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.forename: Michael A
authors.initials: MA
authors.lastname: Choti
authors.forename: Luis A
authors.initials: LA
authors.lastname: Diaz
mesh_terms: D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics*; D005260:Female; D017491:Genes, APC; D016158:Genes, p53; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins