Overexpression of MutL homolog 1 and MutS homolog 2 proteins have reversed prognostic implications for stage I-II colon cancer patients

Biomed J. 2017 Feb;40(1):39-48. doi: 10.1016/j.bj.2017.01.004. Epub 2017 Mar 14.

Abstract

Background: The outcome of colon cancer patients without lymph node metastasis is heterogeneous. Searching for new prognostic markers is warranted.

Methods: One hundred twenty stage I-II colon cancer patients who received complete surgical excision during 1995-2004 were selected for this biomarker study. Immunohistochemical method was used to assess p53, epidermal growth factor receptor, MLH1, and MSH2 status. KRAS mutation was examined by direct sequencing.

Results: Thirty three patients (27.5%) developed metachronous metastasis during follow up. By multivariate analysis, only female gender (p = 0.03), high serum carcinoembryonic antigen (CEA) level (≧5 ng/ml) (p = 0.04), and MLH1 overexpression (p = 0.003) were associated with the metastasis group. The 5-year-survival rate were also significantly lower for female gender (71.7% versus 88.9%, p = 0.025), high CEA level (64.9% versus 92.4%, p < 0.001), and MLH1 overexpression (77.5% versus 94.4%, p = 0.039). In contrast, MSH2 overexpression was associated with better survival, 95.1% versus 75.5% (p = 0.024).

Conclusions: The reversed prognostic implications in the overexpression of MLH1 and MSH2 for stage I-II colon cancer patients is a novel finding and worthy of further confirmation.

Keywords: CEA; Colon cancer; MLH1; MSH2; Mismatch repair.

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Colonic Neoplasms / diagnosis*
  • Colonic Neoplasms / genetics*
  • DNA Repair / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • MutL Protein Homolog 1 / genetics
  • MutL Protein Homolog 1 / metabolism*
  • MutS Homolog 2 Protein / genetics
  • MutS Homolog 2 Protein / metabolism*
  • Mutation / genetics*
  • Neoplasm Metastasis / genetics
  • Neoplasm Staging / methods
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Prognosis
  • Survival Rate

Substances

  • Nuclear Proteins
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein