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 IC(50), 11.2 and 2.75 microM). 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.
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 IC(50), 11.2 and 2.75 microM). 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 cancerpatients treated with cisplatin-based therapy.
Authors: Yin Wu; Marshall R Posner; Lisa M Schumaker; Nikolaos Nikitakis; Olga Goloubeva; Ming Tan; Changwan Lu; Sana Iqbal; Jochen Lorch; Nicholas J Sarlis; Robert I Haddad; Kevin J Cullen Journal: Cancer Date: 2011-08-25 Impact factor: 6.860
Authors: B J Vesper; A Onul; G K Haines; G Tarjan; J Xue; K M Elseth; B Aydogan; M B Altman; J C Roeske; W A Paradise; H De Vitto; J A Radosevich Journal: Tumour Biol Date: 2012-12-14
Authors: Luciane R Cavalli; Yan-Gao Man; Arnold M Schwartz; Janice D Rone; Ying Zhang; Cicero A Urban; Rubens S Lima; Bassem R Haddad; Patricia E Berg Journal: Cancer Genet Cytogenet Date: 2008-11