Expression of DNA repair proteins, MSH2, MLH1 and MGMT in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients' survival

J Oral Pathol Med. 2011 Mar;40(3):218-26. doi: 10.1111/j.1600-0714.2010.00945.x. Epub 2010 Oct 1.

Abstract

Background: DNA repair is a major defense mechanism, which contributes to the maintenance of genetic sequence, minimizing cell death, mutation rates, replication errors, DNA damage persistence and genomic instability. Alterations of proteins participating in DNA repair mechanisms have been associated with several aspects of cancer biology. The present study aimed to evaluate the clinical significance of DNA repair proteins, MSH2, MLH1 and MGMT in mobile tongue squamous cell carcinoma (SCC).

Methods: MSH2, MLH1 and MGMT protein expression was assessed immunohistochemically on 49 mobile tongue SCC tissue samples and was analyzed in relation with clinicopathological characteristics, overall and disease-free patients' survival.

Results: MSH2 expression was significantly associated with depth of invasion (P=0.0335), tumor shape (P=0.0396) and muscular invasion (P=0.0098). MLH1 expression was significantly associated with lymph node metastases (P=0.0484) and borderline with perineural invasion (P=0.0699). MGMT expression was significantly associated with depth of invasion (P=0.0472), tumor shape (P=0.0187), perineural invasion (P=0.0115) and lymph node metastases (P=0.0032) and borderline with vascular invasion (P=0.0755). MSH2 expression was significantly associated with disease-free patients' survival in univariate analysis (P=0.0441), being also identified as an independent prognostic factor in multivariate analysis (P=0.0451).

Conclusions: The present study supported evidence for possible implication of MSH2, MLH1 and MGMT proteins in the formation and progression of mobile tongue SCC.

MeSH terms

  • Adaptor Proteins, Signal Transducing / analysis*
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / secondary
  • Cell Nucleus / pathology
  • DNA Modification Methylases / analysis*
  • DNA Repair / genetics*
  • DNA Repair Enzymes / analysis*
  • Disease Progression
  • Disease-Free Survival
  • Epithelium / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Leukocytes, Mononuclear / pathology
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Mitotic Index
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein / analysis*
  • Neoplasm Invasiveness
  • Nuclear Proteins / analysis*
  • Protein Subunits / analysis*
  • Sex Factors
  • Survival Rate
  • Tongue / pathology
  • Tongue Neoplasms / pathology*
  • Tumor Suppressor Proteins / analysis*

Substances

  • Adaptor Proteins, Signal Transducing
  • MLH1 protein, human
  • Nuclear Proteins
  • Protein Subunits
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • DNA Repair Enzymes