Overexpression of H-Ryk in epithelial ovarian cancer: prognostic significance of receptor expression.
H-Ryk is an atypical receptor tyrosine kinase that is expressed in a differentiation-specific manner in epithelial tissues. We have previously shown by in situ hybridization and immunohistochemistry that H-Ryk is overexpressed in malignant ovarian tumors. In addition, we have demonstrated that overexpression of H-Ryk is transforming in vitro and in vivo. To evaluate whether expression of H-Ryk is a prognostic factor in epithelial ovarian cancer, we carried out a retrospective study of 88 primary malignant ovarian tumors (28 serous tumors, 11 mucinous tumors, 29 endometrioid tumors, 13 clear cell tumors, 3 malignant mixed Mullerian tumors, 1 mixed epithelial tumor, 1 primary peritoneal tumor, 1 undifferentiated tumor, and 1 transitional carcinoma) diagnosed between 1990 and 1993 using immunohistochemistry. On univariate analysis, overall survival decreased significantly with age (P = 0.01); in patients with International Federation of Gynecology and Obstetrics (FIGO) stage II (P = 0.008), FIGO stage III (P < 0.001), and FIGO stage IV (P < 0.001) disease; and in patients with residual disease (residual disease < or = 2 cm, P = 0.007; residual disease > 2 cm, P < 0.001) after surgery. In addition, overexpression of the H-Ryk receptor in malignant epithelium (P = 0.04) and blood vessel (P = 0.01) was associated with a significantly decreased overall survival. H-Ryk blood vessel overexpression (P = 0.03), residual disease > 2 cm (P = 0.006), and residual disease < or = 2 cm (P = 0.01) conferred a significantly shorter progression-free survival. No correlation was found between H-Ryk overexpression and age, histological subtype, degree of differentiation, FIGO stage, or residual disease. Overall, after adjustment for all of the prognostic factors by multivariate analysis (Cox proportional hazards model), residual disease was the most powerful prognostic indicator for overall survival (P < 0.001) and progression-free survival (P = 0.01) in this patient subset. This implies that H-Ryk acts cooperatively with other biological factors in the pathogenesis of ovarian cancer.
Katso
R M
RM
Imperial Cancer Research Fund Molecular Oncology Laboratories, Institute of Molecular Medicine, Oxford, United Kingdom.
Manek
S
S
Ganjavi
H
H
Biddolph
S
S
Charnock
M F
MF
Bradburn
M
M
Wells
M
M
Ganesan
T S
TS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D004730:Endothelium, Vascular / Q000201:enzymology; D004848:Epithelium / Q000201:enzymology; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012189:Retrospective Studies; D017154:Stromal Cells / Q000201:enzymology; D016019:Survival Analysis
C080836:RYK protein, human; D020794:Receptor Protein-Tyrosine Kinases