title: Rectal cancer: the influence of tumor proliferation on response to preoperative irradiation.
abstract: OBJECTIVE
  Regression of rectal carcinoma after preoperative irradiation is variable, likely reflecting differences in the physical and biologic properties of these tumors. This study examines the association between the pathologic response of rectal cancer after irradiation and its pretreatment proliferative state as assayed by the activity of the proliferative dependent antigens (Ki-67, PCNA) and mitotic counts.
  
  
  METHODS
  One hundred and twenty-two patients with locally advanced rectal cancer received preoperative irradiation followed by surgery. Pretreatment tumor biopsies were scored for the extent of Ki-67 and PCNA immunostaining and the number of mitoses per 10 high-powered fields. Postirradiation surgical specimens were examined for extent of residual disease.
  
  
  RESULTS
  The tumors of 38 of 122 patients (31%) exhibited marked pathologic downstaging (no residual tumor or cancer confined to the rectal wall) after preoperative irradiation. Two features were associated with the likelihood of marked pathologic regression after preoperative irradiation: tumor proliferative activity and lesion size. When stratified by lesion size, marked tumor regression occurred most frequently in smaller tumors with high Ki-67, PCNA, and mitotic activity compared to larger tumors with lower Ki-67, PCNA, and mitotic activity. Intermediate downstaging rates were seen for small or large tumors with moderate Ki-67, PCNA, and mitotic activity.
  
  
  CONCLUSIONS
  Tumor Ki-67, PCNA, and mitotic activity predicts the likelihood of response to irradiation, which may aid in formulating treatment policies for patients with rectal cancer.
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: Willett
authors.forename: G
authors.initials: G
authors.lastname: Warland
authors.forename: J
authors.initials: J
authors.lastname: Coen
authors.forename: P C
authors.initials: PC
authors.lastname: Shellito
authors.forename: C C
authors.initials: CC
authors.lastname: Compton
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D009363:Neoplasm Proteins / Q000032:analysis*; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis*; D011300:Preoperative Care; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*; D012004:Rectal Neoplasms / Q000737:chemistry / Q000473:pathology* / Q000532:radiotherapy*
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen