Association of GSTP1 expression with resistance to docetaxel and paclitaxel in human breast cancers.
OBJECTIVE
It has been reported that glutathione S-transferase P1 (GSTP1) expression is implicated in resistance to taxanes (docetaxel and paclitaxel) in human breast cancer cells in vitro. In the study presented here, we examine whether GSTP1 expression is associated with resistance to docetaxel or paclitaxel in human breast cancers. We also investigated the relationship between GSTP1 methylation status and response to these taxanes.


METHODS
Sixty two primary breast cancer patients were treated with docetaxel or paclitaxel as primary systemic treatment (PST). GSTP1 expression was detected immunohistochemically and the hypermethylation status GSTP1 gene was identified with a methylation specific primer assay.


RESULTS
The mean tumor reduction rate for all patients (n=62) was significantly (p<0.001) higher in GSTP1 negative (0.73+/-0.04; mean+/-standard error) than GSTP1 positive (0.31+/-0.09) tumors. The subset analysis showed that the mean reduction rate was significantly (p=0.005) higher in GSTP1 negative (0.59+/-0.06) than GSTP1 positive (0.11+/-0.13) tumors in the docetaxel group as well as in the paclitaxel group (p=0.006; GSTP1 negative tumors: 0.84+/-0.05; GSTP1 positive tumors: 0.56+/-0.08). On the other hand, GSTP1 methylation showed no significant association with the reduction rate.


CONCLUSIONS
Our present study has suggested that GSTP1 protein expression, but not GSTP1 methylation status, might be associated with response to docetaxel and paclitaxel. This suggests that GSTP1 immunohistochemical expression might be a potentially clinically useful predictive factor for response to docetaxel and paclitaxel.
Arai
T
T
Department of Surgical Oncology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-shi, Osaka 565-0871, Japan.
Miyoshi
Y
Y
Kim
S J
SJ
Akazawa
K
K
Maruyama
N
N
Taguchi
T
T
Tamaki
Y
Y
Noguchi
S
S
D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019175:DNA Methylation; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017239:Paclitaxel / Q000493:pharmacokinetics / Q000494:pharmacology*; D043823:Taxoids / Q000493:pharmacokinetics / Q000494:pharmacology*
D000970:Antineoplastic Agents; D005819:Genetic Markers; D043823:Taxoids; D000077143:Docetaxel; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D017239:Paclitaxel