Prevalence and prognostic influence of genomic changes of EGFR pathway markers in synovial sarcoma

J Surg Oncol. 2011 Jun;103(8):773-81. doi: 10.1002/jso.21852. Epub 2011 Jan 15.

Abstract

Background: We aimed to study the prevalence and prognostic influence of epidermal growth factor receptor (EGFR) and its downstream effectors in synovial sarcoma (SS).

Objectives and methods: The tissue blocks from 30 patients were obtained. Expression of EGFR and phosphatase and tensin homolog (PTEN) were examined by immunohistochemistry, and mutation status of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) exon 2, V-raf murine sarcoma viral oncogene homolog B1 (BRAF) exon 15, phosphoinositide-3-kinase, catalytic, alpha polypeptide (PI3KCA) exons 9, 20, and PTEN exons 5-9 were analyzed by direct sequencing.

Results: EGFR overexpression and PTEN deletion were found in 63.3% and 46.7% of patients. Sequence analysis failed to demonstrate mutations of KRAS and BRAF. However, an E545A point mutation in exon 9 of PI3KCA was found in 2 of the 30 (6.7%) cases and 4 point mutations in exon 5 (E99K, D106N), intro 6 to exon 7 (AATA(G)), and exon 9 (A359T) of PTEN were found in 2 of the 30 (6.7%) cases. PTEN loss was significantly more frequent in cases of trunk tumors, and the overexpression of EGFR was significantly more prevalent in patients who were 35 or older.

Conclusions: PTEN deletion was associated with poor survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Child
  • Class I Phosphatidylinositol 3-Kinases
  • DNA Mutational Analysis
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Exons
  • Female
  • Gene Deletion
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutation
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Prevalence
  • Prognosis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins B-raf / metabolism
  • Proto-Oncogene Proteins p21(ras)
  • Sarcoma, Synovial / metabolism*
  • Sarcoma, Synovial / mortality*
  • Sequence Analysis, Protein
  • Soft Tissue Neoplasms / metabolism*
  • Soft Tissue Neoplasms / mortality*
  • Survival Analysis
  • Young Adult
  • ras Proteins / genetics
  • ras Proteins / metabolism

Substances

  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • ErbB Receptors
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins