Mib-1 proliferation index is an independent predictor of lymph node metastasis in invasive breast cancer: A prospective study on 675 patients

Abstract

Abstract. In order to evaluate the potential risk factors for Lymph node metastasis in invasive breast cancer patients submitted to axillary dissection, 675 patients who received surgery between January 1995 and December 2002 were included in a prospective study. In all cases, MIB-1 proliferation index was investigated by immunohistochemistry. Lymph node involvement was found in 248 out of 675 patients. Univariate analysis showed that peritumoral lymphovascular invasion, pT stage, tumor multiplicity, MIB-1 proliferation index >10%, oestrogen receptor status, histological type, tumor grade and progesterone receptor status were related to a higher incidence of Lymph node metastasis, with various levels of statistical significance. Multivariate analysis identified lymphovascular invasion [relative risk (RR, 7.69; p<0.001), pT stage (RR, 3.08; p<0.001), tumor multiplicity (RR, 3.89; p<0.001), and MIB-1 proliferation index (RR, 1.66; p=0.019)] as independent predictive variables. The impact of MIB-1 positivity on the incidence of Lymph node metastasis was particularly evident in intermediate risk groups (pT1c, pT2 without lymphovascular invasion), as well as in grade-2 tumors. In conclusion, the MIB-1 proliferation index could provide additional information about the risk of Lymph node metastasis in invasive breast cancer, and may be useful to identify grade-2 tumors with a more aggressive clinical behaviour. IntroductionNodal status is a strong prognostic factor in breast cancer and is one of the most important variables considered in deciding on adjuvant treatment after surgery. Sentinel node biopsy, although not the standard of care, is rapidly becoming widely accepted as an alternative staging procedure for the axilla in breast cancer. However, in subgroups of patients with a high risk of Lymph node metastasis, this procedure may not provide a clinical benefit and may involve a waste of resources as, in a high percentage of cases, it is followed by axillary dissection. The definition of tumor characteristics that are predictive of Lymph node metastasis may be useful in order to better select which patients to submit to axillary surgery (1).Besides commonly used pathological factors, cell proliferation has an important role as an indicator of biological aggressiveness in breast cancer. Ki-67 antibody reacts with a nuclear antigen which is present in G1, S, G2 phases and mitosis but is absent in G0 and is therefore considered a marker of the proliferative activity of the tumor (2). Unfortunately, the epitope that recognizes Ki-67 is destroyed in the fixation and paraffin embedding process. More recently, the MIB-1 antibody, which recognizes Ki-67 antigen in formalin-fixed, paraffin-embedded tissue, has been described and applied to breast cancer (3,4).Several studies have investigated the role of the proliferation index in breast cancer patients and a strong correlation between the MIB-1 labelling index and Lymph node metastasis has been reported (5,6), although this finding has not been confirmed by others (7-10)....

Prognostic value of Ki67 analysed by cytology or histology in primary breast cancer

“…Furthermore, these findings are supported by the results showing that tumours with ‘high’ Ki67 in tumour resections had a significantly higher probability for lymph node metastasis. Similar findings were reported by Marrelli et al ,41 although a lower cut-off for high proliferation (≥10%) was used 41. High proliferation by Ki67 evaluated on whole sections and tissue microarrays has been associated with lymph node metastasis 40.…”

Hormone Receptor Status Rather Than HER2 Status Is Significantly Associated With Increased Ki-67 and p53 Expression in Triple-Negative Breast Carcinomas, and High Expression of Ki-67 but Not p53 Is Significantly Associated With Axillary Nodal Metastasis in Triple-Negative and High-Grade Non–Triple-Negative Breast Carcinomas

“…Some previous studies revealed that a high Ki-67 expression level was associated with more frequent lymph node metastasis in patients with all types of breast cancer, but they did not investigate an association between p53 expression and nodal metastasis. 7,25,26 Our findings demonstrated that a high expression level of Ki-67 (>10%) but not p53, although both are considered prognostic markers for breast cancer, was significantly associated with axillary nodal metastasis in patients with TN and high-grade non-TN tumors, indicating that Ki-67 has a better prognostic value than p53 for these breast carcinomas. Previous studies have demonstrated that TN breast tumors are more frequently associated with lymph node metastasis compared with non-TN tumors.…”

Cell kinetics and gene expression changes in colorectal cancer patients given resistant starch: a randomised controlled trial

“…MIB1 (mindbomb homologue 1 ( Drosophila )), a monoclonal antibody against the Ki-67 antigen (1:250 dilution), was used to identify proliferating cells within the tumour tissue. The proliferating cell index (PCI) of the tumours was estimated by examining the stained slides using a square graticule at high magnification (×100) as described previously 24 25…”