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[Cancer Research 63, 8097-8102, December 1, 2003]
© 2003 American Association for Cancer Research

Advances in Brief

Glutathione S-Transferase {pi} Amplification is Associated with Cisplatin Resistance in Head and Neck Squamous Cell Carcinoma Cell Lines and Primary Tumors

Kevin J. Cullen12, Kenneth A. Newkirk12, Lisa M. Schumaker1, Naji Aldosari13, Janice D. Rone13 and Bassem R. Haddad13

1 Department of Oncology, Lombardi Cancer Center, Washington, DC;
2 Department of Otolaryngology, Medstar-Georgetown University Hospital, Washington, DC; and
3 Institute for Molecular and Human Genetics, Lombardi Cancer Center, Washington, DC

Purpose: The purpose is to evaluate the association of glutathione S-transferase {pi} (GST-{pi}) amplification and cisplatin resistance in head and neck cancer.

Experimental Design: An analysis of chromosomal abnormalities in 10 head and neck cancer cell lines by comparative genomic hybridization was performed. GST-{pi} amplification and expression were evaluated in head and neck cell lines and paraffin-embedded tissue by fluorescence in situ hybridization (FISH) and immunohistochemistry.

Results: Changes in the DNA copy number were seen in all 10 cell lines by comparative genomic hybridization. The most frequent chromosomal alterations were: gain at 3q; loss at 3p; gain at 8q; loss of 18q; gain at 20q; loss at 8p; and gain of 11q11-q13. Using FISH, 9 of 10 cell lines showed increased GST-{pi} copy number. GST-{pi} amplification was detected in 7 of 10 cell lines. Five were relatively cisplatin resistant, and 2 were relatively cisplatin sensitive (mean IC50, 11.2 and 2.75 µM). Two relatively cisplatin-sensitive cell lines showed GST-{pi} gain and another relatively cisplatin-sensitive cell line had predominantly two copies of the gene. In 10 tumor specimens, 4 had two copies of GST-{pi}. All 4 had a complete response to neoadjuvant chemotherapy, 3 of whom are alive >50 months from treatment compared with 2 patients showing GST-{pi} amplification. Neither responded to chemotherapy, and both died of disease <9 months from diagnosis.

Conclusions: Using FISH, GST-{pi} amplification is a common event in head and neck squamous cell carcinoma and may be associated with cisplatin resistance and poor clinical outcomes in head and neck cancer patients treated with cisplatin-based therapy.




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