A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance is a common complication of HIV protease inhibitors. Diabetes mellitus is relatively uncommon.

Experimental laboratory data suggest that tumour growth is a balance between apoptosis and proliferation and that suppression of drug-induced apoptosis by oncogenes such as bcl-2 may be an important cause of intrinsic chemoresistance. The aims of this study were to assess the in vivo relationship of apoptosis to proliferation and Bcl-2 protein in human breast tumours both prior to chemotherapy and in the residual resistant cell population at the completion of treatment. We examined apoptotic index (AI), Ki67 and Bcl-2 protein expression in the tissue of 40 patients with operable breast cancer immediately before ECF preoperative chemotherapy, and in 20 of these patients with residual tumour, at the completion of treatment. There was a significant positive association between AI and Ki67 both before and after chemotherapy, and in their percentage change with treatment. In the residual specimens AI and Ki67 were significantly reduced compared with pre-treatment biopsies, while Bcl-2 expression showed a significant increase. No differences were seen in the pre-treatment levels of any of the variables measured between patients obtaining pathological complete response and those who did not, although numbers were small. These data suggest that apoptosis and proliferation are closely related in vivo. It is possible that the phenotype of reduced apoptosis and proliferation, and increased Bcl-2 may be associated with breast cancer cells resistant to cytotoxic chemotherapy, although this can only be proven by assessing larger numbers of patients in relation to pathological response.

Summary The MIB-l antibody has been raised against recombinant parts of the Ki-67 antigen and, unlike Ki-67, has wider application to routinely fixed specimens. The aim of this study was to compare the usefulness of MIB-l with S-phase fraction (SPF) as a measure of proliferation. A total of 75 patients with operable breast cancer were studied, 44 (median age 56 years) before any treatment and 31 (median age 68 years) after primary medical hormonal therapy. Sections from formalin-fixed paraffin-embedded tissue were stained with the MIB-1 antibody and a percentage score of positively stained cells obtained. SPF was measured by flow cytometry in fine-needle aspiration samples taken from the same lesion in each patient. Median MIB-1 score was 9% and median SPF was 1. 1%. A close correlation was found between MIB-1 score and SPF (rho = 0.59, P < 0.0001). There was a difference in the strength of the correlation found between the no treatment group and the treatment group, however, 95% confidence intervals for the rho values overlapped, indicating that there was no significant statistical difference. When analysed for ploidy status a correlation was found only in aneuploid tumours. MIB-l immunostaining can be used as an effective method of assessing proliferation in human breast carcinomas. This can be done using simple, widely available technology and provides the opportunity to perform large-scale retrospective analyses of archival material.

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