ABSTRACT
We examined the correlation between response to platinum-based chemotherapy and expression of glutathione S-transferase (GST), gamma-GGT (both by immunohistochemistry) and gamma-GCS (by in situ hybridization) in 51 patients with head and neck cancer, who received a total of 56 courses of chemotherapy. The overall response rate for the 56 chemotherapy treatment courses was 48%. The overall response rate (CR, PR) for patients with low GST scores was 88% (21 of 24), while among the patients with high GST scores, the overall response rate was 19% (6 of 32, P = 0.001). Patients with a low GST score were 4.7 times more likely to respond to chemotherapy than patients with high GST scores. GST scores corresponded to response in 84% of cases. Among 33 patients treated with chemotherapy for relapsed disease, the overall response rate for patients with low GST score was 70% (7 of 10), while among the patients with high GST scores, the overall response rate was 8.7% (2 of 23), P < 0.001). In contrast, both gamma-GCS and gamma-GGT showed a range of expression in these samples, but there was no significant correlation with treatment response. We conclude that GST expression correlates well with response to platinum based chemotherapy in head and neck cancer.
Subject(s)
Antineoplastic Agents/therapeutic use , Glutathione/metabolism , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/metabolism , Platinum Compounds/therapeutic use , Aged , Female , Gene Expression , Glutamate-Cysteine Ligase/genetics , Glutathione Transferase/metabolism , Head and Neck Neoplasms/enzymology , Humans , Immunohistochemistry , In Situ Hybridization , Male , Middle Aged , Retrospective Studies , gamma-Glutamyltransferase/metabolismABSTRACT
The glutathione S-transferases (GSTs) play an important role in the cell's defense against toxic substances. The GSTs are a family of enzymes produced by several genes that interact with distinct but overlapping substrates and that may play a role in resistance of tumor cells to several chemotherapeutic agents. We examined the correlation between expression of GSTs determined by immunohistochemistry and clinical response to platinum-based chemotherapy in 51 patients with head and neck cancer, who received a total of 56 courses of chemotherapy. The overall response rate for the 56 chemotherapy treatment courses was 48%. The overall response rate (complete response + partial response) for patients with low GST scores was 88% (21 of 24), whereas among the patients with high GST scores, the overall response rate was 19% (6 of 32; P = 0.001). Patients with a low GST score were 4.7 times more likely to respond to chemotherapy than patients with high GST scores. GST scores corresponded to response in 84% of cases. Among 23 patients treated with neoadjuvant chemotherapy, the overall response rate for patients with low GST scores was 100% (14 of 14), whereas among the patients with high GST scores, the overall response rate was 44% (4 of 9; P = 0.002). Among 33 patients treated with chemotherapy for relapsed disease, the overall response rate for patients with low GST scores was 70% (7 of 10), whereas among the patients with high GST scores, the overall response rate was 8.6% (2 of 23; P < 0.001). We conclude that GST expression correlates well with response to platinum-based chemotherapy in head and neck cancer.
