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

M.C. González-Vela, M.F. Garijo, F. Fernández and J.F. Val-Bernal

Anatomical Pathology Department, "Marqués de Valdecilla" University Hospital, Medical Faculty, University of Cantabria, Santander, Spain

Offprint request to: Dr. J. Fernando Val-Bernal, Departamento de Anatomía Patológica, Hospital Universitario Marqués de Valdecilla, Avda. Valdecilla 1, E-39008 Santander, Spain. Fax: +34 942 201903. e-mail: apavbj@humv.es

Summary. Aims: In breast invasive carcinoma our objectives were I) to compare cellular proliferation determined by MIB1 index with S-phase fraction (SPF) assessed by flow cytometry and with mitotic index, and II) to examine the association of MIB1 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-µm 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. MIB1 index was correlated with SPF (rho=0.45, p<0.0001) 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). MIB1 was associated directly with p53 (p=0.045) and inversely with bcl-2 (p=0.0002). The MIB-1 index was not statistically associated with c-erbB-2. There was a weak association between MIB1 index and stromal cell CD. The median MIB1 index was higher in tumors with moderate to strong CD staining of stromal cell, but the difference did not reach statistical significance (p=0.09). Conclusions: MIB1 index correlates with well established methods for assessing tumor proliferation and with parameters of an aggressive phenotype of tumor. MIB1 index is an effective and readily accessible method for assessing tumor proliferation in breast carcinoma. Histol. Histopathol. 16, 399-406 (2001)

Key words: Breast carcinoma, MIB-1, Oncogene, Proliferation, Cathepsin D

DOI: 10.14670/HH-16.399