M6P/IGF2R loss of heterozygosity in head and neck cancer associated with poor patient prognosis

BMC Cancer. 2003 Feb 13;3:4. doi: 10.1186/1471-2407-3-4. Epub 2003 Feb 13.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Controlled Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / therapy*
  • Female
  • Genetic Predisposition to Disease
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Loss of Heterozygosity*
  • Male
  • Middle Aged
  • Receptor, IGF Type 2 / genetics*
  • Survival Analysis
  • Treatment Failure
  • Treatment Outcome

Substances

  • Receptor, IGF Type 2