Protein expression and prognostic value of genes in the erb-b signaling pathway in advanced ovarian carcinomas

Am J Clin Pathol. 2005 Sep;124(3):392-401. doi: 10.1309/BL7E-MW66-LQX6-GFRP.

Abstract

By using tissue microarrays and immunohisto-chemical analysis, we studied protein expression of genes in the erb-b signaling pathway (erb-b1; erb-b2; phosphoinositide-3-kinase, catalytic, a polypeptide [PIK3CA]; phosphatase and tensin homologue [PTEN]; phosphorylated AKT [p-AKT]; and phosphorylated extracellular signal-regulated kinase [p-ERK]) in 118 advanced ovarian carcinomas and related expression to clinicopathologic features and survival. High protein expression was seen in 15.3% of cases for erb-b2, 44.1% for erb-b1, 43.2% for PIK3CA, 51.6% for p-AKT, and 28.0% for p-ERK. Low protein levels of PTEN were seen in 41.5% of the cases and tended to be more common in well-differentiated tumors. In multivariate analysis, only high expression of both erb-b1 and erb-b2 was an independent factor in progression-free and disease-specific survival (P=.009, hazard ratio=2.46; P=.002, hazard ratio=3.023, respectively). The PI3K/AKT and RAS/MEK/ERK pathways seem to be activated in some cases of advanced ovarian carcinomas, although PIK3CA, p-AKT, p-ERK, and PTEN do not seem to be independent prognostic markers in this group of patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Class I Phosphatidylinositol 3-Kinases
  • ErbB Receptors / analysis
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Ovarian Neoplasms / chemistry*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • PTEN Phosphohydrolase
  • Phosphatidylinositol 3-Kinases / analysis
  • Phosphoric Monoester Hydrolases / analysis
  • Prognosis
  • Protein Serine-Threonine Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-akt
  • Receptor, ErbB-2 / analysis
  • Signal Transduction*
  • Tumor Suppressor Proteins / analysis

Substances

  • Proto-Oncogene Proteins
  • Tumor Suppressor Proteins
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • ErbB Receptors
  • Receptor, ErbB-2
  • AKT1 protein, human
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase
  • PTEN protein, human