B7-H4 is over-expressed in early-stage ovarian cancer and is independent of CA125 expression

Abstract

Objective This study characterizes the expression of the novel biomarker B7-H4 in ovarian cancer tissue, normal ovaries, and benign ovarian tumors, and evaluates its relationship to CA125. Methods Ovarian tissue lysates from 251 patients with ovarian carcinoma were assessed for the levels of B7-H4 and CA125 by ELISA assays. For comparison, ovarian tissues from patients with benign ovarian tumors ( n = 43) and patients with normal ovaries ( n = 32) were tested. The marker concentrations were correlated with CA125 expression, clinicopathological variables, and patient outcome. Results Using a cut-off based on the 95th percentile of B7-H4 or CA125 concentration in the control group, B7-H4 was over-expressed in 48% of patients with stage I cancer, 55% of patients with stage II cancer, and 67% of patients with late stage cancer. CA125 was elevated in 31% patients with early stage cancer. B7-H4 was elevated in tumors of 30 patients with early stage cancer that were negative for CA125. The combination of B7-H4 and CA125 identified 56 early stage cancer patients (65%) as positive. Correlation of marker expression to clinical outcome showed that high B7-H4 levels were correlated with poor prognosis. However, the effect was not significant when outcome was adjusted for other clinicopathological variables. Conclusion B7-H4 expression was low in normal ovaries and in benign tumors while half of early stage and two-thirds of late stage cancers over-expressed B7-H4. The data are consistent with previous observations and support further investigation of B7-H4 in the detection of early stage ovarian cancer either alone, or in combination with CA125.