ErbB-3 predicts survival in ovarian cancer.
BACKGROUND
HER3 (erbB-3) is a member of the epidermal growth factor receptor (EGFR) family. After dimerization with other members of the EGFR family several signal transduction cascades can be activated, including phosphoinosite 3'-kinase (PI3-K)/Akt and extracellular signal-regulated kinase (ERK1/2). Here, we studied a possible association between HER3 expression and prognosis in patients with ovarian cancer.


METHODS
Tumor tissue of 116 consecutive patients diagnosed with primary epithelial ovarian cancer between 1986 and 1995 was analyzed immunohistochemically for HER3 expression. A possible influence of HER3 expression on survival was studied by multivariate Cox regression adjusting for established clinical prognostic factors.


RESULTS
A positive HER3 expression was observed in 53.4% of the patients. HER3 expression was associated with decreased survival in proportional hazard modeling, including the International Federation of Gynecology and Obstetrics (FIGO) stage, histologic grade and type, residual disease, and age. After likelihood ratio forward as well as backward selection, only HER3 expression (hazard ratio, 1.71; 95% CI, 1.10 to 2.67; P = .018), FIGO stage (hazard ratio, 4.78; 95% CI, 1.89 to 12.08; P = .001), residual tumor (hazard ratio, 2.69; 95% CI, 1.40 to 5.17; P = .003), and age (hazard ratio, 2.06; 95% CI, 1.17 to 3.65; P = .013) were found to be significant. Kaplan-Meier plots demonstrated a clear influence of HER3 expression on survival time. Median survival time was 3.31 years (95% CI, 1.93 to 4.68) for patients with low HER3 expression, compared with only 1.80 years (95% CI, 0.83 to 2.78) for patients with HER3 overexpression (log-rank test P = .0034).


CONCLUSIONS
HER3 may represent a new prognostic factor in primary epithelial ovarian cancer. Pending validation, exploration of therapeutic strategies to block HER3 could be warranted.
Tanner
Berno
B
Department of Gynecology and Obstetrics, University of Mainz, Mainz, Germany.
Hasenclever
Dirk
D
Stern
Katja
K
Schormann
Wiebke
W
Bezler
Martin
M
Hermes
Matthias
M
Brulport
Marc
M
Bauer
Alexander
A
Schiffer
Ilka B
IB
Gebhard
Susanne
S
Schmidt
Markus
M
Steiner
Eric
E
Sehouli
Jalid
J
Edelmann
Jeanett
J
Läuter
Jürgen
J
Lessig
Rüdiger
R
Krishnamurthi
K
K
Ullrich
Axel
A
Hengstler
Jan Georg
JG
D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D020893:Receptor, ErbB-3 / Q000032:analysis*; D016019:Survival Analysis; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3