title: Immunocytochemical study of Ki-67 as a prognostic marker in canine mammary neoplasia.
abstract: BACKGROUND
  Canine mammary tumors are challenging for clinicians and pathologists because of complex histologic classification, low specificity of cytologic diagnosis, and unpredictable biological behavior. In histologic specimens, expression of tumor proliferation marker Ki-67, a nuclear nonhistone protein, has been shown to have prognostic value for canine mammary tumors and to correlate with malignancy and low survival rates.
  
  
  OBJECTIVE
  The objective of this study was to measure the proliferation index of canine mammary tumors by immunochemical detection of Ki-67 in cytologic specimens and to determine its relationship to clinical and pathologic variables and patient outcome.
  
  
  METHODS
  Spontaneous mammary tumors from 31 female dogs were surgically excised. Imprint specimens for cytologic evaluation were wet-fixed in ethanol; histologic specimens were prepared routinely. Immunostaining was performed with the PH 177 monoclonal antibody against Ki-67; proliferation index was graded from negative to +++. Dogs were followed for 18 months. Multivariate logistic regression analysis was used to determine correlations between immunocytochemical results, tumor and clinical variables, and patient outcome.
  
  
  RESULTS
  Ki-67 proliferation indices in cytologic specimens were significantly lower for nonmalignant tumors than for malignant tumors. High index values of Ki-67 were positively correlated with metastasis, death from neoplasia, low disease-free survival rates, and low overall survival rate. With the exception of 4 specimens for which cellularity was insufficient, positive expression of Ki-67 in cytologic specimens correlated with that of histologic specimens.
  
  
  CONCLUSIONS
  The prognostic value of the Ki-67 index in canine mammary tumors by using wet-fixed cytology imprint specimens was similar to that observed previously for histologic specimens. Immunocytochemical detection of Ki-67 could improve the accuracy and value of cytology by providing safe and rapid information about malignancy and patient outcome.
authors.affiliation: Clinics and Surgery Department, FCAV, UNESP, Jaboticabal (SP), Brazil. debora.zuccari@terra.com.br
authors.forename: Debora A P C
authors.initials: DA
authors.lastname: Zuccari
authors.forename: Aureo E
authors.initials: AE
authors.lastname: Santana
authors.forename: Patrícia M
authors.initials: PM
authors.lastname: Cury
authors.forename: José Antônio
authors.initials: JA
authors.lastname: Cordeiro
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000032:analysis*; D004283:Dog Diseases / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D004285:Dogs; D005260:Female; D005500:Follow-Up Studies; D007150:Immunohistochemistry / Q000662:veterinary*; D019394:Ki-67 Antigen / Q000032:analysis*; D008321:Mammary Glands, Animal / Q000473:pathology; D015674:Mammary Neoplasms, Animal / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen