CDMRP Investigator Vignette

Title: Prevention of Ovarian High-Grade Serous Carcinoma by Elucidating Its Early Changes

Investigators: Ie-Ming Shih, M.D., Ph.D., Robert Kurman, M.D., Johns Hopkins University

Shih: The ovarian cancer research team at Hopkins was recently awarded by the DoD Ovarian Cancer Consortium Award and the main focus is to identify and to delineate the pathogenesis of the early ovarian cancer-how it develops and what kind of molecular changes that can affect the genesis of ovarian cancer. So, we have 5 projects and I'm the leader of the Project 1, which tried to focus on the presumable precursor of ovarian cancer. We call it STIC-it's for the serous tubal intraepithelial carcinoma, STIC. And based on our previous study and the many studies from other research groups, we found that the STICs represent most likely the precursor addition of ovarian cancer.

So in that way ovarian cancer is not what we think-it's coming from the ovary, but we think it's an imported disease. It's imported from the fallopian tube, so this STIC as its name implies is coming from the fallopian tube. Then it spread onto the ovary and where it forms a big ovarian mass. And we think well, it's ovarian cancer, but in fact it's coming from the fallopian tube.

So this kind of very novel concept deserves a lot of work to test the hypothesis whether this origin of ovarian cancer coming from the fallopian tube is real. If this is real, it will have a huge impact on the patient's care in terms of prevention, treatment, and the diagnosis.

Kurman: We tend to use the term "paradigm shift," it's almost cliche, but I think it really does appropriately describe what was going on in our understanding of ovarian cancer. So that is what really convinced us that we should try to create this consortium and try to understand more about the early events responsible for the development of ovarian cancer.

The consortium consists of Hopkins, which is the coordinating center and where the three cores are. There's a pathology core, an administration core, and a biostatistics epidemiology core. Then the other institutions are Memorial Sloan-Kettering in New York City, University of Toronto in Toronto, and Yale. So Hopkins is the coordinating center, has the cores, has some research studies, and the other institutions are research sites.

And the idea of the core is that-ovarian cancer is a highly lethal disease. It's the most lethal of all the female reproductive cancers and far more lethal than breast cancer. So in order to collect a sufficient number of specimens to really understand the disease so that you have what we call statistical power, you need to accumulate a certain number of patients and tissue materials.

And since any one institution just doesn't collect enough of these, the idea was by creating a consortium that this-this data, the patient data could be pooled and create a large enough database that would be-so experiments, studies could be done, larger number of-of patients that would end up providing significant results.

Shih: So we collaborate with those investigators to contribute the STICs specimens and try to centralize through Hopkins for us to do cell studies. And the studies include molecular genetic studies, meaning we micro-dissect the precursor lesion and compare the genetic content with the ovarian high-grade serous carcinoma. And we also perform the [teenko] pathological features to see how can we tell the pathologists how can we make a better diagnosis of the STIC because at this moment the diagnosis of STIC is very subjective and there's no criteria.

So one of the immediate goals of our consortium is to set the criteria; how can we call this STIC or not STIC and I think it's a very important foundation for the success of this Consortium Award.

Kurman: Dr. Shih and I have collaborated now for probably not quite 20 years. We've written many, many papers together. My training is focused on looking at microscopic slides. Dr. Shih works in the laboratory and focuses on analyzing the molecular genetics. I as a pathologist can indirectly analyze that with certain special stains under the microscope but really the important cutting-edge discoveries of what those genetic changes are that play a role in these early events of ovarian cancer really come out of the laboratory where Dr. Shih works.

By bringing different disciplines, by bringing the epidemiologists, by bringing the biostatisticians, by bringing in the molecular biologists and the pathologists and the gynecologist, you get a full picture of the disease. So I think collaborative research is really the way to go.

Shih: Because of this DoD Consortium we can develop new investigators who are willing to be devoted to ovarian cancer research, and we can also disseminate the knowledge to other investigators .

I think it's just like a snowball. And it's generated more and more ovarian cancer researchers-bringing more people into this field because of the seed which is the OCRP.