Comparison of monoclonal antibody Ki-67 reactivity with grade and DNA flow cytometry of breast carcinomas

Abstract

Summary The reactivity of 95 breast carcinomas with the antibody Ki-67, which recognises a nuclear antigen in proliferating cells, has been assessed and compared to their histological grade and, for 47 tumours, DNA index and S-phase content. The effects of freezing and section handling on the stability of the nuclear antigen have been assessed.Evidence of nuclear staining was seen in 56% of carcinomas, with a range of positive cells from <1% to 60%. Cytoplasmic rather than nuclear staining was observed in 26% and 18% of carcinomas were negative. A significant correlation was observed between the presence of nuclear staining and poorer histological grade and higher S-phase content, and between the percentage of positive nuclei and S-phase content, but not grade. Three groups of carcinomas were identified: those in which Ki-67 reactivity, grade and S-phase content were similar; ones in which there was prominent nuclear reactivity with Ki-67 but low grade and S-phase content; and a group showing the converse. These patients will be followed to assess which of these three markers of proliferation is of greatest prognostic value.

Assessment of the new proliferation marker MIB1 in breast carcinoma using image analysis: associations with other prognostic factors and survival

“…The strong association between the extent of nuclear area staining with MIBI antibody and histological grade is similar to that we have reported previously with Ki-67 (Bouzubar et al, 1989) and which has been noted by others (Walker and Camplejohn, 1988;Betta et al, 1989;Wrba et al, 1989;Dawson et al, 1990). This correlation with histological grade is strong; however, in multivariate analysis MIBI labellng is of indepenent prognostic sign .…”

“…In breast carcinomas, although some have found no association between Ki-67 immunoreactivity and other prognostic variables (Stumpp et al, 1992), many authors have reported an association with histological grade (Walker and Camplejohn, 1988;Betta et al, 1989;Bouzubar et al, 1989;Wrba et al, 1989;Dawson et al, 1990). Associations with lymph node status (Wrba et al, 1989), patient's age (Sahin et al, 1991), tumour size (Wrba et al, 1989;Veronese and Gambacorta, 1991), oestrogen and progesterone receptor status (Wrba et al, 1989;Campani et al, 1991;Di-Stefano et al, 1991;Veronese and Gambacorta, 1991), ploidy (Dawson et al, 1990;Isola et al, 1990;Lee et al, 1992), p53 (Barbareschi et al, 1992) (1991) showed that the response to endocrine therapy of a breast carcinoma was related to the degree of Ki-67 immunoreactivity, and an association between Ki-67 staining and both disease-free interval and survival has been reported (Veronese et al, 1993).…”

“…This reacts with a proliferation-associated antigen which is expressed in all cells not in Go phase of the cell cycle. Many authors have produced data suggesting that an assessment of the percentage of cells showing immunoreactivity with Ki-67 antibody correlates with other methods of determining the rate of growth of a malignant tumour such as S-phase fraction assessed by flow cytometry and mitotic count (Walker and Camplejohn, 1988;Dawson et al, 1990;Isola et al, 1990;Kennedy et al, 1992), as well as thymidine labelling index (Karmel et al, 1989) and 5-bromodeoxyuridine labelling (Sasaki et al, 1988). More recently, several other antibodies have been described which have been advocated as effectively demonstrating proliferating cells in formalin-fixed tissue including anti-proliferating cell nuclear antigen (PCNA), Ki-SI and MIBI.…”

Interferon plus tamoxifen treatment for advanced breast cancer: in vivo biologic effects of two growth modulators

“…In vitro studies suggest that the interferons should be useful in the treatment of breast cancer, modulating both tumour The alterations induced by IFN pretreatment on the expression of the proliferation associated antigen Ki 67, which has previously been shown to correlate with mitotic index, 'S' phase fraction and prognosis in breast cancer (Barnard et al, 1987;Walker & Camplejohn, 1988), were those which were predicted from the in vitro anti-proliferative effects of IFN. Both the patients who had initial high Ki 67 expression, showed significant reduction after IFN and both responded to therapy.…”

Cell proliferation measured by MIB1 and timing of surgery for breast cancer

“…A number of studies have found an association between Ki-67 expression and other prognostic variables (Walker and Camplejohn, 1988;Wintzer et al, 1991). Until recently, the most significant limitation to the use of monoclonal Ki-67 was the need for frozen material, as the antigen is very sensitive to fixation and prolonged storage (Neubauer and Hunn, 1987).…”