Protein expression and prognostic value of genes in the erb-b signaling pathway in advanced ovarian carcinomas.
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.
Wang
Yun
Y
Department of Gynecologic Oncology, the Norwegian Radium Hospital and the University of Oslo, Oslo, Norway.
Kristensen
Gunnar B
GB
Helland
Aslaug
A
Nesland
Jahn M
JM
Børresen-Dale
Anne-Lise
AL
Holm
Ruth
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058534:Class I Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors / Q000032:analysis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases / Q000032:analysis; D010744:Phosphoric Monoester Hydrolases / Q000032:analysis; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000032:analysis
D058534:Class I Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D010744:Phosphoric Monoester Hydrolases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D025521:Tumor Suppressor Proteins; C484760:PIK3CA protein, human; C494918:AKT1 protein, human; C494929:PTEN protein, human