An Evaluation of the Molecular Species of CA125 Across the Three Phases of the Menstrual Cycle

ABSTRACTAn Evaluation of the Molecular Species of CA125 Across the Three Phases of the Menstrual CycleCA125, a tumor-associated antigen, is primarily used to monitor epithelial ovarian cancer. However, CA125 alone lacks the sensitivity and specificity necessary for population-based screening in healthy women. Barriers to the development of a screening assay includes the low incidence of the disease, large inter-individual variability in CA125 levels, fluctuations in levels during the phases of the menstrual cycle (i.e., menses, follicular, luteal), ethnicity, menopausal status, and other benign conditions. Evaluation of the molecular species of serum CA125 is a vital step in understanding the underlying biology of CA125. The specific aims of this study, in a sample of healthy women were: 1) To determine if the molecular species of CA125 differ across the three phases of the menstrual cycle; and 2) To determine if the absolute serum concentrations of CA125 differ across the three phases of the menstrual cycle, using two common commercial CA125 assays. Healthy, Caucasian women between the ages of 18 and 39 were enrolled using strict criteria to minimize serum CA125 fluctuations. After menstrual cycle regularity was determined using calendars maintained by participants for 3 months, blood samples for analyses of CA125 were collected at three different phases of the menstrual cycle. Serum levels of CA125 fluctuated across the menstrual cycle, with the highest levels found during menses. The amount of change in CA125 over time (i.e., 0.2 U/ml per day) was identical using both assays, which suggests that the relative changes in CA125 are consistently measured regardless of assay system. Additionally Western blot analysis yielded seventeen distinct profiles (patterns of species) of CA125. Demographic characteristics and serum CA125 values are not significantly different for each CA125 pattern or at any time point. Consistent with previous studies of CA125, our data show species ranging from 31 to 460 kDa. Most of the referent bands in our data appear at 117 kDa or higher indicating that CA125 may primarily be a high molecular weight species in healthy women with regular menstrual cycles. Future research needs to determine the clinical importance and the molecular composition of these species of CA125