MIB1 proliferation index in breast infiltrating carcinoma: Comparison with other proliferative markers and association with new biological prognostic factors

Abstract

Aims: In breast invasive carcinoma our objectives were 1) to compare cellular proliferation determined by MIBl index with S-phase fraction (SPF) assessed by flow cytometry and with mitotic index, and 11) to examine the association of MIBl index with classical and with new biological prognostic factors [bcl- 2, p53, c-erbB-2 and cathepsin D (CD)]. Methods and results: From 102 cases of breast invasive carcinoma, 5- pm thick serial sections were cut from formalin-fixed, paraffin-embedded tissue blocks, and processed for detection of CD, c-erbB-2, p53, bcl-2, Ki-67 antigen MIB-1 and estrogen receptors (ER) and progesterone receptors (PR). SPF was measured by flow cytometry in fresh-frozen tissue samples taken from the carcinoma in each patient. MIBl index was correlated with SPF (rho=0.45, pe0.0001) and with mitotic index (rho=0.42, p<0.0001). The MIB-1 index was positively associated with the histological grade (p=0.001), tumor size (p=0.04) and the presence of metastases in axillary lymph nodes (p=0.01). MIBl was associated directly with p53 (p=0.045) and inversely with bcl-2 @=0.0002). The MIB-1 index was not statistically associated with cerbB- 2. There was a weak association between MIBl index and stromal cell CD. The median MIBl index was higher in tumors with moderate to strong CD staining of stromai cell, but the difference did not reach statistical significance (p=0.09). Conclusions: MIBl index correlates with well established methods for assessing tumor proliferation and with parameters of an aggressive phenotype of tumor. MIBl index is an effective and readily accessible method for assessing tumor proliferation in breast carcinoma.