Localization-specific LKB1 loss in head and neck squamous cell carcinoma metastasis

Head Neck. 2011 Oct;33(10):1501-12. doi: 10.1002/hed.21638. Epub 2010 Dec 9.

Abstract

Background: LKB1 loss is associated with invasive carcinoma and metastasis. In head and neck squamous cell carcinoma (HNSCC), lymph node metastasis status is the strongest predictor of survival.

Methods: LKB1 immunohistochemistry was performed on primary tumors from patients with HNSCC who never developed metastases, patients with metastases, and their paired lymph node metastasis to determine whether LKB1 was associated with HNSCC metastasis.

Results: LKB1 was expressed in the nucleus and cytoplasm of tumor cells and HNSCC cell lines. Primary tumors from patients with metastatic carcinoma had decreased nuclear, but not cytoplasmic, LKB1 compared to patients with nonmetastatic cancer. Nuclear LKB1 levels correlated with lymph node metastasis grade and primary tumor site. The percentage of tumor cells negative for nuclear LKB1 staining was greatest in the primary metastatic tumor group, and decreased nuclear LKB1 trended toward worse disease-free survival.

Conclusion: Decreased nuclear LKB1 levels correlate with HNSCC metastasis and suggest a nuclear function of LKB1 in repressing HNSCC metastasis.

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cytoplasm / metabolism
  • Female
  • Fluorescent Antibody Technique
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Metastasis*
  • Protein Serine-Threonine Kinases / metabolism*

Substances

  • Protein Serine-Threonine Kinases
  • STK11 protein, human
  • AMP-Activated Protein Kinase Kinases