What started as a high school science fair project has developed into groundbreaking preliminary research that could change the way prostate cancer is diagnosed and treated, improving the quality of life for thousands of men who face unnecessary treatment and severe side effects.
The study, which appeared in the American Journal of Clinical Pathology, was authored by 18-year-old Ali Tradonsky and her friend Tammy Rubin.
The two teens worked with Tradonsky's mother, Dr. Sharon Mair, a pathologist and member of the American Society for Clinical Pathology, to identify four genes tied to prostate cancer prognosis.
Tradonsky and Rubin began the study in 2009 with the goal of determining molecular cytogenetic markers that could help differentiate aggressive cases of prostate cancer from indolent cases. "As such, the goal of the study was to discover something new-to make a major breakthrough," Tradonsky told ADVANCE.
While the young researchers realized from the beginning it would be a long shot to choose markers that would end up to be prognostically significant, they knew that even negative results would mean they had eliminated markers that others would need to test. "We took an educated guess and happened to choose the correct genes, and that was our breakthrough," Tradonosky said.
Before launching the project, Mair tasked the young scientists with learning everything there is to know about the prostate gland -- anatomy, physiology, histology and how to grade and stage according to Gleason, as well as cytogenetic marker staining and medical statistics.
The pair identified the study population by working with the tumor registrar; searching patients' histories to find out personal and familial characteristics of importance to the study (e.g., family history with the disease, race, serum PSA levels). They pulled thousands of slides and tissue blocks from hospital storage rooms; graded and staged cases on a double-headed microscope with their advisor; and made note of benign regions which they would later use for comparison as internal controls for every patient.
Throughout this remarkable journey, Tradonsky and Rubin worked closely with, and learned from a group of scientists at the Hudson Alpha institute from Alabama. "We are eternally grateful to these scientists, our coauthors, for affording us the opportunity," Tradonsky said.
The two researchers visited the partner lab to learn how to make tissue microarrays and stain them with appropriate dilutions of specific antibody immunostains; interpreted marker stains; and analyzed their results using numerous statistical methods.
Hoping for Change
"When we first began this project, we knew that we would be investing at least 2 years of our time into it. As such, we decided to do research on something that we had the opportunity to improve. We wanted our project to have a real-world application," Tradonosky noted. "Prostate cancer was the perfect option because it is one of the most prominent cancers in men, and it is the most over treated. Much remains unknown with respect to prognostic markers and monoclonal antibody treatment in prostate cancer. The way society treats prostate cancers now has many unnecessary economic and personal costs, and that was something we hoped we could change."
"We hope that our discoveries can be used in the future to differentiate prostate cancer patients who need treatment from those who can be safely watched," Tradonsky told ADVANCE. "This, in turn, will save many men from unnecessary treatment, negative side effects from treatment and healthcare costs."
And they likely will: One of the four genes in the study, HEY2, shows particular promise as an indicator of aggressive prostate cancer, much as HER2 has been linked to aggressive breast cancer. As with HER2, therapies could be developed to target this form of prostate cancer, which is highly resistant to current therapies.
"If these results are confirmed, we believe a simple kit could be developed to test all four antibodies to those genes," said Omar Hameed, MD, ASCP spokesperson and associate professor and director of surgical pathology, Vanderbilt University Medical Center, Nashville. "This would provide the doctor with a risk assessment tool that could be used to help determine which patients should receive radical treatment and those who can be safely watched with regular prostate specific antigen (PSA) tests."
Tradonsky plans to study economics and medicine, with an eye towards becoming involved in the business side of medicine. She enrolled at the University of Pennsylvania community this fall.
Kerri Hatt is on staff at ADVANCE. She can be reached at firstname.lastname@example.org.