In ovarian cancer the prognostic influence of HER2/neu is not dependent on the CXCR4/SDF-1 signalling pathway.
HER2/neu overexpression is a driving force in the carcinogenesis of several human cancers. In breast cancer the prognostic influence of HER2/neu was shown to be at least partly based on increased metastatic potential mediated by the chemokine-chemokine receptor pair SDF-1(CXCL12)/CXCR4. We wanted to evaluate the influence of HER2/neu on ovarian cancer prognosis and to investigate whether compromised survival would correlate with CXCR4 expression and/or SDF-1 abundance. Therefore, we analysed HER2/neu, CXCR4, and SDF-1 in 148 ovarian tumour samples by means of immunohistochemistry on tissue microarrays. Overexpression of HER2/neu was found in 27.6% of ovarian cancer tissues and in 15% of ovarian borderline tumours. In ovarian cancer patients, overexpression of HER2/neu correlated closely with overall survival (univariate hazard ratio (HR) 2.59, P=0.005; multiple corrected HR 1.92, P=0.074). In contrast, CXCR4 expression and SDF-1 abundance had no impact on overall survival, and both parameters were not correlated with HER2/neu expression. As expected, cytoplasmic CXCR4 expression and SDF-1 abundance correlated closely (P<0.0001). Our results confirm a univariate influence of HER2/neu expression on overall survival, which was completely independent of the expression of CXCR4 and the abundance of SDF-1, implying significant differences between the HER2/neu downstream pathways in ovarian cancer compared with breast cancer.
Pils
D
D
Department of Internal Medicine I, Division of Oncology, Medical University of Vienna, Waehringer Guertel 18-20, Vienna A-1090, Austria.
Pinter
A
A
Reibenwein
J
J
Alfanz
A
A
Horak
P
P
Schmid
B C
BC
Hefler
L
L
Horvat
R
R
Reinthaller
A
A
Zeillinger
R
R
Krainer
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000032:analysis / Q000502:physiology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000401:mortality*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D019718:Receptors, CXCR4 / Q000032:analysis / Q000502:physiology*; D015398:Signal Transduction
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D018719:Erb-b2 Receptor Tyrosine Kinases; D019718:Receptors, CXCR4; C515255:CXCL12 protein, human