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 carcin omas, including measurements of proliferative activity such as mitotic counts, S-phase fraction determination, bromodeoxyuridine labeling, a nd frozen section Ki-67 detection. The MIB-1 antibody reliably detects the Ki-67 antigen in paraffin-embedded tissues and is ideal for use i n routine tissue sections. The proliferation index (PI), defined as th e number of MIB-1-positive tumor cells per 1,000 cell count, was compa red between paraffin sections of low-stage primary breast carcinomas f rom 32 patients who did not develop tumor recurrence over a 5-year per iod and those from 16 women who ultimately did have tumor recurrence. All patients had low-stage primary tumors, defined as Stage 1 or 2A le sions; none received radiation therapy or chemotherapy other than adju vant tamoxifen citrate. Immunohistochemical studies for MIB-1 were per formed using the avidin-biotin complex method on formalin-fixed paraff in-embedded sections with heat-induced epitope unmasking. The PI was s ignificantly higher in primary tumors in patients with (mean PI = 36.7 %) versus without (mean PI = 16.4%) tumor recurrence (p < 0.01). In pa tients with recurrence, PIs of the primary tumors were not significant ly different from those of the recurrent carcinomas. There was a posit ive correlation between the PI and mitotic score per 10 high-power fie ld (HPF) counts (r = 0.56, p < 0.0001), mitotic index /1,000 cells cou nted (r = 0.40, p < 0.01), nuclear grade (r = 0.59, p < 0.0001), degre e of glandular differentiation (r = 0.52, p < 0.0001), and combined tu mor grade (r = 0.63,p < 0.0001). Multivariate analysis comparing mitot ic score, mitotic index, combined histologic grade, stage, and PI, fou nd PI to be the strongest predictor of disease recurrence. Of the seve n patients with a PI greater than or equal to 40, all had disease recu rrence. A high PI, as determined by MIB-1 paraffin section immunohisto chemistry, is a useful predictor of tumor recurrence, within 5 years, in Stages 1 and 2A breast carcinomas.