A Paradigm Shift for Ovarian Cancer Detection: Screening Liquid-Based Pap Tests by Mass Spectrometry
Abstract
Central Problem: Each year more than 21,000 women in the United States are diagnosed with ovarian cancer, primarily with late stages of the disease. Consequently, the 5-year survival rate is only 45%. Early detection of ovarian cancer is the key to better survival rates, yet a screening tool has yet to be developed that is adequately sensitive and specific for the general population. For decades, researchers have been using biospecimens (e.g., blood and tissues) taken from women with late stages of ovarian cancer in an attempt to discover biomarkers that could be used to detect early stages of ovarian cancer. However, it appears that these "late-stage" biomarkers may not be present in biospecimens taken from women with early stages of ovarian cancer. Unfortunately, it has been very difficult to obtain biospecimens from women at early stages of ovarian cancer (i.e., before the women even have symptoms of disease) to use for the first phase of biomarker discovery. Our Solution: In contrast to ovarian cancer, screening for cervical cancer by Pap tests has been routinely performed for over 50 years. The liquid-based Pap test has an easy collection method whereby cervical cells are placed into an alcohol-based fixative and then examined for abnormal cells; occasionally, ovarian cancer cells have been identified in Pap tests. The objective of this study is to discover and verify ovarian cancer biomarkers in Pap test fixative samples from patients at early stages of the disease. At the University of Minnesota, the cytopathologists see over 60,000 Pap tests annually. In our Gynecologic Cancer Clinic, we have been performing "Mock Pap tests" for several years and have accrued hundreds of fixatives and swabs from women with ovarian cancer and other gynecological conditions, as well as healthy women. Since 2011, our collaborators at the Karolinska Institute in Sweden have banked the residual Pap test fixative and cell pellets from most of the women who have had a Pap test, resulting in a collection of over 340,000 banked samples. Of these samples, over 700 per year are from women who were then diagnosed with ovarian cancer; their tumors have been subsequently banked as well. In this study, our group will be the first to analyze the residual Pap test fixative by proteomic techniques for the discovery and verification of early-stage ovarian cancer protein biomarkers. Our central hypothesis is that proteins and small peptides shed by ovarian cancer cells can be detected in the residual Pap test fixative by mass spectrometry-based proteomics. Rationale: The Pap test fixative is ideal for the discovery phase of early-stage biomarker development, since it is derived from a site near the ovarian cancer (i.e., proteins may be secreted or shed from the tumor and flow through the fallopian tube into the uterus and out the cervical opening). Several recent studies have shown that tumor-specific biomarkers are present at higher levels in biospecimens that are proximal to the tumor itself, as compared to blood samples. Recently, the fimbria of the fallopian tube has been suggested to be the true precursor to ovarian and primary peritoneal carcinomas, strengthening our hypothesis. As proof-of-principle, our preliminary data demonstrate that Pap test fixatives can be used to detect known ovarian cancer biomarkers in women with late-stage ovarian cancer. Furthermore, it contains fewer high abundance proteins, which have hampered biomarker discovery studies with blood samples. Long-Term Goal: Our long-term goal is to develop an easy, noninvasive screening test that can be readily incorporated into a routine Pap test so that women can be tested simultaneously for cervical and ovarian cancer. The ultimate goal of this research is to develop a highly sensitive test for the detection of ovarian cancer in its early stages when treatments are most effective; this goal is in line with Ovarian Cancer Research Program s mission to "
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610070
Entities
People
- Amy P N Skubitz
Organizations
- United States Army
- University of Minnesota