The ErbB signalling pathway: protein expression and prognostic value in epithelial ovarian cancer.
Ovarian cancer is the most frequent cause of death from gynaecological cancer in the Western world. Current prognostic factors do not allow reliable prediction of response to chemotherapy and survival for individual ovarian cancer patients. Epidermal growth factor receptor (EGFR) and HER-2/neu are frequently expressed in ovarian cancer but their prognostic value remains unclear. In this study, we investigated the expression and prognostic value of EGFR, EGFR variant III (EGFRvIII), HER-2/neu and important downstream signalling components in a large series of epithelial ovarian cancer patients. Immunohistochemical staining of EGFR, pEGFR, EGFRvIII, Her-2/neu, PTEN (phosphatase and tensin homologue deleted on chromosome 10), total and phosphorylated AKT (pAKT) and phosphorylated ERK (pERK) was performed in 232 primary tumours using the tissue microarray platform and related to clinicopathological characteristics and survival. In addition, EGFRvIII expression was determined in 45 tumours by RT-PCR. Our results show that negative PTEN immunostaining was associated with stage I/II disease (P=0.006), non-serous tumour type (P=0.042) and in multivariate analysis with a longer progression-free survival (P=0.015). Negative PTEN staining also predicted improved progression-free survival in patients with grade III or undifferentiated serous carcinomas (P=0.011). Positive pAKT staining was associated with advanced-stage disease (P=0.006). Other proteins were expressed only at low levels, and were not associated with any clinicopathological parameter or survival. None of the tumours were positive for EGFRvIII. In conclusion, our results indicate that tumours showing negative PTEN staining could represent a subgroup of ovarian carcinomas with a relatively favourable prognosis.
de Graeff
P
P
Department of Gynaecologic Oncology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, Groningen 9713 GZ, The Netherlands.
Crijns
A P G
AP
Ten Hoor
K A
KA
Klip
H G
HG
Hollema
H
H
Oien
K
K
Bartlett
J M
JM
Wisman
G B A
GB
de Bock
G H
GH
de Vries
E G E
EG
de Jong
S
S
van der Zee
A G J
AG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D004847:Epithelial Cells / Q000473:pathology; D066246:ErbB Receptors / Q000096:biosynthesis / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016896:Treatment Outcome
D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D051058:Oncogene Protein v-akt; D051059:PTEN Phosphohydrolase; D018719:Erb-b2 Receptor Tyrosine Kinases; C410723:epidermal growth factor receptor VIII; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C494929:PTEN protein, human