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The value of assessing cell proliferation in breast cancer
1University Department of Virology, University Medical School, Sheffield, U.K.
Abstract:
Using three methods to measure cell proliferation, namely DNA cell cycle; anti-proliferating cell monoclonal antibody (MAb) (Ki67, P145) analysis by flow cytometry; and the histological silver (argyrophilic) staining technique to visualize nuclear-organizing regions (AgNOR), twenty-two paired samples of primary breast tumour and axillary lymph node were analysed. The results showed variable levels of correlation between the methods used for the tumour group (r = 0.915, P less than 0.001 for Ki677 versus P145; r = 0.42, P less than 0.005 for percentage S/G2/M-phase versus P145; r = 0.16, P less than 0.5 for percentage S/G2/M-phase versus AgNOR; r = 0.400, P less than 0.1 for Ki67 versus AgNOR). The lymph-node group showed slightly poorer correlations, yet involved nodes showed a consistently higher level of proliferation than non-involved nodes by all methods used. Overall, MAb binding of Ki67 or P145 was seen to be a good indicator of cycling cells, detecting G1-phase cells in addition to S/G2/M-phase cells identified by the other methods used. However, no advantage was found over the usual DNA flow cytometric analysis of cells, which had clear prognostic value. AgNOR scores were found to be able to discriminate between diploid and aneuploid; and dividing and non-dividing cells, but areas of score overlap limited the application of this technique to that of a positive discriminator only.