M6P/IGF2R loss of heterozygosity in head and neck cancer associated with poor patient prognosis
1 Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA
2 Southeast Georgia Regional Medical Center, Radiation Oncology Center, Brunswick, GA, USA
3 Laboratory of Pathology, National Institutes of Health, Bethesda, MD, USA
4 Department of Gastroenterology, Chikushi Hospital, Fukuoka University, Fukuoka, Japan
5 Department of Radiation Oncology, Uijongbo St. Mary's Hospital, Uijongbo, Korea
6 Department of Radiation Oncology, Cancer Hospital, Fudan University, Shanghai, P.R. China
7 Department of Pathology, VA Medical Center, Durham, NC, USA
BMC Cancer 2003, 3:4 doi:10.1186/1471-2407-3-4Published: 13 February 2003
The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) encodes for a multifunctional receptor involved in lysosomal enzyme trafficking, fetal organogenesis, cytotoxic T cell-induced apoptosis and tumor suppression. The purpose of this investigation was to determine if the M6P/IGF2R tumor suppressor gene is mutated in human head and neck cancer, and if allelic loss is associated with poor patient prognosis.
M6P/IGF2R loss of heterozygosity in locally advanced squamous cell carcinoma of the head and neck was assessed with six different gene-specific nucleotide polymorphisms. The patients studied were enrolled in a phase 3 trial of twice daily radiotherapy with or without concurrent chemotherapy; median follow-up for surviving patients is 76 months.
M6P/IGF2R was polymorphic in 64% (56/87) of patients, and 54% (30/56) of the tumors in these informative patients had loss of heterozygosity. M6P/IGF2R loss of heterozygosity was associated with a significantly reduced 5 year relapse-free survival (23% vs. 69%, p = 0.02), locoregional control (34% vs. 75%, p = 0.03) and cause specific survival (29% vs. 75%, p = 0.02) in the patients treated with radiotherapy alone. Concomitant chemotherapy resulted in a better outcome when compared to radiotherapy alone only in those patients whose tumors had M6P/IGF2R loss of heterozygosity.
This study provides the first evidence that M6P/IGF2R loss of heterozygosity predicts for poor therapeutic outcome in patients treated with radiotherapy alone. Our findings also indicate that head and neck cancer patients with M6P/IGF2R allelic loss benefit most from concurrent chemotherapy.