Clinical impact of c-MET expression and genetic mutational status in colorectal cancer patients after liver resection

Cancer Sci. 2014 Aug;105(8):1002-7. doi: 10.1111/cas.12453. Epub 2014 Aug 7.

Abstract

c-MET is implicated in the pathogenesis and growth of a wide variety of human malignancies, including colorectal cancer (CRC). The aim of the present study was to clarify the association between c-MET expression and tumor recurrence in CRC patients after curative liver resection, and to evaluate concordance in c-MET expression and various mutations of KRAS, BRAF and PIK3CA between primary CRC and paired liver metastases. A cohort of patients was tested for c-MET immunoreactivity (i.e. immunohistochemistry [IHC]) and KRAS, BRAF and PIK3CA mutations. Analyses were performed both on primary tumors and paired liver metastases, and the association between IHC and mutations results were assessed. A total of 108 patients were eligible. A total of 53% of patients underwent simultaneous resection of primary tumors and metastases, and the others underwent metachronous resection. Levels of concordance between primary tumors and metastases were 65.7%, 87.7%, 100% and 95.2% for c-MET, KRAS, BRAF and PIK3CA, respectively. High levels of c-MET expression (c-MET-high) in the primary tumors were observed in 52% of patients. Relapse-free survival was significantly shorter for patients with c-MET-high primary tumors (9.7 months) than for those with c-MET-low primary tumors (21.1 months) (P = 0.013). These results suggest that a high level of genetic concordance in KRAS, BRAF and PIK3CA between primary tumors and liver metastases, and c-MET-high in the primary tumors were associated with shorter relapse-free survival after hepatic metastasectomy.

Keywords: Colorectal cancer; c-MET expression; genetic mutational status; hepatic metastasectomy; relapse-free survival.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Class I Phosphatidylinositol 3-Kinases
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • DNA Mutational Analysis
  • Disease-Free Survival
  • Female
  • Hepatectomy
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / metabolism*
  • Phosphatidylinositol 3-Kinases / genetics
  • Proportional Hazards Models
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins c-met / biosynthesis*
  • Proto-Oncogene Proteins p21(ras)
  • Young Adult
  • ras Proteins / genetics

Substances

  • Biomarkers, Tumor
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • Proto-Oncogene Proteins c-met
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins