Nuclear morphometry and glutathione S-transferase pi expression in breast cancer

Glutathione S-transferase pi (GST-pi) is a phase TI detoxification enzyme w hose expression is increased in estrogen receptor (ER)-poor breast cancers and in breast cancers resistant to certain chemotherapeutic agents. The aim of this study was to investigate the immunohistochemical expression of GST -pi in invasive breast carcinoma and to correlate the findings with those o f nuclear morphometry. Formalin-fixed paraffin-embedded tissue specimens ob tained from 21 invasive breast cancers and 16 adjacent (benign) tissues wer e immunohistochemically stained using polyclonal anti-human GST-pi antibody . There was positive (defined as >10% immunoreactive tumor cells) but varia ble expression of GST-pi in 10 (48%) cases. Nuclear morphometry in these 10 tumors revealed immunoreactive malignant cells to be larger (mean area 41. 7+/-1.0 mu m(2)) and more rounded in form when compared with non-staining c ancer cells (mean area 28.7+/-0.7 mu m(2)). It was also observed that GST-p i immunonegative tumor cells in GST-pi expressing tumors had different morp hologies from malignant cells in the remaining 11 (52%) cancers that were r egarded as GST-pi negative. Increased GST-pi. expression determined by the percentage of positively staining tumor cells, was found to be significantl y correlated with increased variability in nuclear area and perimeter (Spea rman's e=0.821, p=0.044 for both) in the subset of node-positive tumors. Ou r findings suggest that there exists two sub-populations of cancer cells wi th distinct nuclear morphologies in GST-pi positive tumors; factors other t han GST-pi expression are likely to have a phenotypic effect on breast canc er cells; and there may be a special significance of this enzyme in axillar y node-positive breast tumors.