Researchers from Rush University Medical Center and Harborview Medical Center at University of Washington have identified biomarkers that may lead to earlier identification of those at risk for ovarian cancer. Based on previous epidemiologic studies showing that women with infertility problems and women with ovarian cancer have autoantibodies to ovarian antigens, Dr Judith L. Luborsky, associate director for basic research at Rush University Cancer Center and professor in the departments of pharmacology, obstetrics and gynecology, and preventive medicine at Rush University Medical Center, and colleagues explored the possibility that women with infertility problems have antibodies to the well-characterized ovarian cancer antigen mesothelin.
Luborsky and colleagues looked at sera from patients with infertility (n = 109), healthy women (n = 152), patients with ovarian cancer (n = 28), and benign ovarian tumors or cysts (n = 24). The researchers also used 16 serum controls to assess nonspecific serum reactions and to determine a cutoff value for a positive result. Sera mesothelin levels were measured using standard sandwich immunoassay.
Compared to healthy women, the researchers found significantly higher serum mesothelin antigen levels in women with ovarian cancer, benign conditions, and unexplained infertility. Luborsky and colleagues further noted that mesothelin antibodies had a higher affinity in the infertility groups, especially premature ovarian failure and ovulatory dysfunction, than that in the healthy, benign, or ovarian cancer groups. Specifically, they found significantly higher positive sera in women with premature ovarian failure and ovulatory dysfunction as compared to normal sera. However, the number of positive sera found in the unexplained fertility, endometriosis, or benign conditions did not differ from normal sera.
“This study extends previous studies which showed that women with infertility and women with ovarian cancer have antibodies to ovarian antigens and shows for the first time that women with specific categories of infertility have antibodies to a well-known ovarian cancer biomarker,” the researchers explained.
Although the researchers did not examine the specific relationship between the biomarker and the progression of the disease, they do have some theories. “It has been hypothesized that an autoimmune response precedes or somehow contributes to the development and progression of malignant tumors,” Luborsky told the press. “We think that antibodies may arise in response to very early abnormal changes in ovarian tissue that may or may not progress to malignancy, depending on additional triggering events. Or, alternatively, antibodies may bind to normal cells in the ovary, causing dysfunction and leading to infertility—and, in a subpopulation of women, to the development of ovarian cancer.”
“The finding is extremely important because at present medical tests are unable to detect ovarian cancer in its early stages, which is why death rates from this disease are so high,” Luborsky added. “With the discovery of the mesothelin antibody, we now have what appears to be a biomarker that can potentially be used in screening tests to help us conquer ovarian cancer.”
Luborsky JL, Yu Y, Edassery SL, et al. Autoantibodies to mesothelin in infertility. Cancer Epidemiol Biomarkers Prev. 2011 August 16 [Epub].
Rush News Room. Researchers at Rush University Medical Center Discover Antibody That May Help Detect Ovarian Cancer in its Earliest Stages. Rush University Medical Center News Releases. August 17, 2011.