Intratumoural heterogeneity of proliferation in invasive breast carcinoma evaluated with MIB1 antibody

The growth fraction has been assessed in 120 cases of primary operable breast carcinoma using the MIB1 antibody and an index of the cycling fraction has been derived for the periphery and the centre of different histological types of breast cancer. The mean MIB1 labelling index for each tumour showed a strong association with histological grade (P < 0.001), tumour type sub-group (P < 0.001), tumour size (P = 0.029), the presence of vascular invasion (P = 0.050) and the presence of distant metastases (P = 0.043). In addition both the peripheral (P = 0.005) and mean (P = 0.048) but not the central (P = 0.069) MIBI labelling showed a correlation with overall survival, when those cases in the upper quartile were compared with those showing fewer cycling cells. A significantly greater MIB1 labelling index was seen at the periphery than the centre (P < 0.001). This difference in the cycling fraction was not associated with a bias in tumour grade or size. When the data were analysed according to tumour type it was seen that in invasive ductal/no special type (NST) of grades 2 and 3, tubular mixed and lobular carcinomas the peripheral index was significantly higher than the central index (P = 0.002, P = 0.003, P = 0.024 and P = 0.004 respectively). No significant difference in peripheral and central proliferation index was seen in tubular, medullary and atypical medullary or mixed NST and lobular carcinomas (P = 0.480, P = 0.089, P = 0.069 respectively). When tumours were grouped into 3 categories according to the ratio of MIB1 labelling (i.e. those with (i) relatively greater central, (ii) relatively greater peripheral and (iii) homogeneous cell cycling fractions), it was found that the central index was comparable (P = 0.243). Peripheral MIB1 immunostaining was however significantly different (P = 0.049) in the three groups. Thus, the heterogeneity in proliferation seen in this series was not apparently caused by a relative fall in proliferation in the centre of the tumour but to a relative increase in cell cycling fraction at the periphery.