The important prognostic value of Ki-67 expression as determined by image analysis in breast cancer

Abstract

A series of 191 female breast carcinomas (with long-term follow-up) were analysed immunohistochemically (with a monoclonal MIB1 antibody) for Ki-67 (a proliferation marker) expression with special reference to well-established prognostic factors and patient survival. Expression of Ki-67 was directly related to the S-phase fraction (P < 0.0001), the volume-corrected mitotic index (P < 0.0001), histological grade (P < 0.0001), the apoptotic index (P < 0.0001), oestrogen and progesterose receptor content (P < 0.0001 for both) and p53 accumulation (P = 0.001). No correlation was found between Ki-67 expression and lymph node status (P = 0.25), metastasis at operation (n = 0.81) or tumour size (n = 0.38). The proliferation rate, as measured by image analysis of Ki-67 expression, predicted survival in the entire cohort (P = 0.001) and in axillary-lymph-node-negative (ANN) patients (P = 0.003). The difference in recurrence-free survival between the high- and low-expression groups was greatest in ANN tumours, 40% (P = 0.008). In axillary-lymph-node-positive tumours, the Ki-67 expression was not significantly related to recurrence-free survival (P = 0.723). The results of multivariate survival analysis showed that tumour size, axillary lymph node status, and mitotic index were independent prognostic factors in the entire series whereas, in ANN cases, tumour size and Ki-67 labelling were independent prognostic factors. These findings imply that Ki-67 expression could be an important prognostic determinant in breast cancer. Because of the evident loss of the predictive power of tumour size in the 1990s, the prognostic value of Ki-67 expression may even be accentuated in the currently diagnosed small breast carcinomas.

Deregulation of cyclin E and D1 in breast cancer is associated with inactivation of the retinoblastoma protein

“…Our ®nding of seven immunohistochemical pRB defect out of 79 examined tumours (9%) is somewhat lower than in other studies in breast cancer (Varley et al, 1989;Sawan et al, 1992;PietilaÈ inen et al, 1995) where frequencies have been between 20 and 30% using the same technique. These di erences could be caused by various immunostaining methods and evaluation procedures.…”

MIB-1 labelling index is an independent prognostic marker in primary breast cancer

“…In our study we found a significant influence of MIB-1 on disease-free survival in nodenegative, but not node-positive patients. Comparable results have been found in two other studies (Pietilainen et al, 1996;Querzoli et al, 1996), whereas one study has demonstrated an effect of MIB-1 on disease-free survival for both groups of patients (Seshadri et al, 1996). A difference in the prognostic value of MIB-1 for nodenegative and node-positive patients could be explained by more susceptibility for adjuvant (chemo)therapy in node-positive patients with high MIB-1 labelling index, whereas node-negative patients were not treated by adjuvant systemic therapy.…”

“…In general, the MIB-1 index also seems to be a prognostic factor sometimes even in multivariate analyses, but follow-up is generally rather short and/or the number of patients is low (Jensen et al, 1995;Domagala et al, 1996;Seshadri et al, 1996;Pietilainen et al, 1996;Veronese et al, 1996). Not many studies have been performed comparing the different methods of assessing the proliferative activity of a tumour.…”

Apoptosis in breast cancer: relationship with other pathological parameters.

“…AI was 4.5(0.5)/mm 2 , compared with 15.4(1.1)/mm 2 in tumours with a mitotic index greater than 10/mm 2 (P<0.0001) . Other indicators of cell proliferation, such as Ki67 expression (Pietiläinen et al 1996, Ellis et al 1998, van Slooten et al 1998, also have been found to be highly significantly related to AI, in studies based on image analysis (Pietiläinen et al 1996) or conventional light microscopy (Ellis et al 1998, van Slooten et al 1998. In a series of 49 breast carcinomas, 84% of tumours in which the proportion of Ki67-positive cells was less than 20% also had an AI below the median value (0.77%); 61% of tumours in which there was more than 20% of Ki67-positive cells had AIs greater than that median value (P=0.001) (van Slooten et al 1998).…”