Association between serum levels of soluble tumor necrosis factor receptors/CA 125 and disease progression in patients with epithelial ovarian malignancy: a gynecologic oncology group study.
BACKGROUND
A prospective study was undertaken within the Gynecologic Oncology Group to determine whether serum levels of soluble tumor necrosis factor receptors I (sTNFR-I) and II (sTNFR-II), alone or in combination with CA 125, were associated with clinicopathologic characteristics or outcome in patients with epithelial ovarian malignancies.


METHODS
Quantitative immunoassays were performed on valid pretreatment serum specimens obtained from patients with epithelial ovarian malignancies to assess levels of sTNFR-I, sTNFR-II, and CA 125. The authors then analyzed the results of these immunoassays for potential correlations with clinicopathologic characteristics and outcome.


RESULTS
The median age of the 139 women evaluated was 59 years. Seventy-eight percent had Stage III or IV disease, and 58% had serous carcinomas. sTNFR-II was associated with age (P = 0.013), and CA 125 was associated with histologic subtype (P = 0.0009). In addition, sTNFR-I (P = 0.037) and CA 125 (P < 0.0001) were associated with extent of disease. After adjusting for patient age, histologic subtype, and extent of disease, all three biomarkers were predictive of progression-free survival, but not overall survival, when the combination was included in the model. The authors observed a 51% reduction (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.24-0.99), a 2.9-fold increase (HR, 2.87; 95% CI, 1.15-7.20), and a 22% increase (HR, 1.22; 95% CI, 0.99-1.51) in the risk of progression for each unit increase in the log-transformed levels of sTNFR-I, sTNFR-II, and CA 125, respectively.


CONCLUSIONS
The observations made in the current study-that among patients with low or high CA 125 levels, those with high sTNFR-I levels and low sTNFR-II levels had the lowest risk, that patients with low-low or high-high sTNFR-I and sTNFR-II levels, respectively, had an intermediate risk, and that patients with low sTNFR-I levels and high sTNFR-II levels had the highest risk of progression-suggested the potential value of simultaneous assessment of all three biomarkers in patients with epithelial ovarian malignancies.
Burger
Robert A
RA
Department of Obstetrics and Gynecology, University of California-Irvine Medical Center, Orange, CA, USA.
Darcy
Kathleen M
KM
DiSaia
Philip J
PJ
Monk
Bradley J
BJ
Grosen
Elizabeth A
EA
Gatanaga
Tetsuya
T
Granger
Gale A
GA
Wang
Jianmin
J
Tian
Chunqiao
C
Hanjani
Parviz
P
Cohn
David E
DE
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D018394:CA-125 Antigen / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D000068800:Etanercept; D005260:Female; D049669:History, 16th Century; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000401:mortality / Q000473:pathology; D010051:Ovarian Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept