Glutathione S-transferase pi (GST-pi), a Phase II detoxification
enzyme, has recently been implicated in protection against apoptosis. Expression of GST-pi and Bcl-2
protein, an established apoptosis marker, was analyzed by immunohistochemistry in 116 cases of infiltrative ductal
breast carcinomas in Singapore women. The markers were correlated with apoptosis detected by the TUNEL method and clinico-pathological parameters. There were 67 (58%) GST-pi-positive
breast tumors and 43 (37%) Bcl-2-positive
tumors. In a large proportion of GST-pi-positive/Bcl-2-positive
tumors, there was a distinct accumulation of the GST-pi
enzyme within the nucleus of
cancer cells when examined by double immunofluorescence labeling under confocal microscopy. GST-pi immunoreactivity was not significantly correlated with any of the traditional histologic factors known to influence prognosis, whereas Bcl-2 overexpression was associated with reduced size of primary
tumor (P =.021) and positive
estrogen receptor status (P =.001). Univariate analysis revealed that GST-pi-positive, Bcl-2-positive, and lower histological grade
tumors had decreased levels of apoptosis (P =.024, P =.011, and P =.029, respectively). However, multivariate analysis showed that histological grade and Bcl-2, but not GST-pi, immunoreactivity were correlated with apoptotic status. The Kaplan-Meier disease-free survival curves showed a significant difference between GST-pi-positive and GST-pi-negative
breast cancer cases (P =.002). Disease-free survival in patients with GST-pi-positive
tumors was also worse than that in patients with GST-pi-negative
tumors in the group who had
adjuvant chemotherapy (P =.04). In patients who were lymph node positive, GST-pi immunopositivity was found to influence disease-free survival. Recurrence of
tumors was also significantly affected by GST-pi immunoreactivity (relative risk of 8.1). The findings indicate that GST-pi-positive
tumors are more aggressive and have a poorer prognosis than do corresponding GST-pi-negative breast
cancers.