Correlation among MIB-1, paraffin section proliferation index, and recurrence in low-stage breast carcinoma

A multitude of prognostic factors have been proposed for breast carcinomas, including measurements of proliferative activity such as mitotic counts, S-phase fraction determination, bromodeoxyuridine labeling, and frozen section Ki-67 detection. The MIB-1 antibody reliably detects the Ki-67 antigen in paraffin-embedded tissues and is ideal for use in routine tissue sections. The proliferation index (PI), defined as the number of MIB-1-positive tumor cells per 1,000 cell count, was compared between paraffin sections of low-stage primary breast carcinomas from 32 patients who did not develop tumor recurrence over a 5-year period and those from 16 women who ultimately did have tumor recurrence. All patients had low-stage primary tumors, defined as Stage 1 or 2A lesions; none received radiation therapy or chemotherapy other than adjuvant tamoxifen citrate. Immunohistochemical studies for MIB-1 were performed using the avidin-biotin complex method on formalin-fixed paraffin-embedded sections with heat-induced epitope unmasking. The PI was significantly higher in primary tumors in patients with (mean PI = 36.7%) versus without (mean PI = 16.4%) tumor recurrence (p < 0.01). In patients with recurrence, PIs of the primary tumors were not significantly different from those of the recurrent carcinomas. There was a positive correlation between the PI and mitotic score per 10 high-power field (HPF) counts (r = 0.56, p < 0.0001), mitotic index /1,000 cells counted (r = 0.40, p < 0.01), nuclear grade (r = 0.59, p < 0.0001), degree of glandular differentiation (r = 0.52, p < 0.0001), and combined tumor grade (r = 0.63,p < 0.0001). Multivariate analysis comparing mitotic score, mitotic index, combined histologic grade, stage, and PI, found PI to be the strongest predictor of disease recurrence. Of the seven patients with a PI greater than or equal to 40, all had disease recurrence. A high PI, as determined by MIB-1 paraffin section immunohistochemistry, is a useful predictor of tumor recurrence, within 5 years, in Stages 1 and 2A breast carcinomas.