title: Cell proliferation in breast cancer is a major determinant of clinical outcome in node-positive but not in node-negative patients.
abstract: The growth rate of a tumor cell population depends on two major factors: the percentage of proliferating cells (cell growth fraction) and the rapidity of their duplication (cell proliferation rate). The authors evaluated the prognostic and predictive value of both kinetics parameters in a large series of breast cancer patients (n=504). The cell growth fraction was determined by MIB-1 immunostaining, the cell proliferation rate by AgNOR analysis. Ki-67 LI (labeling index) and AgNOR area were significantly associated with histotype, histologic grade, tumor size, estrogen/progesterone receptor status, patient age, and lymph node involvement (P<0.005). In the entire series of patients, both kinetics variables were significantly and independently associated with the clinical outcome, but their prognostic relevance was quite different when node-negative and node-positive patients were considered separately. Although in node-positive patients Ki-67 LI and AgNOR area were the unique independent predictors of disease-free and overall survival, they were excluded by the multivariate Cox model in node-negative patients, where only tumor size and estrogen receptor status retained a significant P-value. These results show that in breast carcinoma the cell growth fraction and the cell proliferation rate have a different prognostic impact with respect to the lymph node status and are major determinants of clinical outcome in node-positive patients only. Within this subgroup, the rapidity of cell proliferation as assessed by AgNOR analysis also served as a sensitive predictor of the response to adjuvant treatments.
authors.affiliation: Department of Experimental Pathology, Unit of Clinical Pathology, University of Bologna, Italy. davide.trere@unibo.it
authors.forename: Davide
authors.initials: D
authors.lastname: Treré
authors.forename: Claudio
authors.initials: C
authors.lastname: Ceccarelli
authors.forename: Mario
authors.initials: M
authors.lastname: Migaldi
authors.forename: Donatella
authors.initials: D
authors.lastname: Santini
authors.forename: Mario
authors.initials: M
authors.lastname: Taffurelli
authors.forename: Elena
authors.initials: E
authors.lastname: Tosti
authors.forename: Pasquale
authors.initials: P
authors.lastname: Chieco
authors.forename: Massimo
authors.initials: M
authors.lastname: Derenzini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000401:mortality* / Q000473:pathology; D002277:Carcinoma / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology*; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor