Study Explains High Platelets in Ovarian Cancer Patients; Survival Reduced

Highly elevated platelet levels fuel tumor growth and reduce the survival of ovarian cancer patients, an international team of researchers led by scientists at The University of Texas MD Anderson Cancer center reports in the New England Journal of Medicine.

By pinpointing a powerful cause-and-effect relationship at the heart of a clinical observation that dates back more than 100 years, the team's findings reveal a new factor in cancer progression and new potential approaches for treatment.

"We've long known that ovarian cancer patients often have markedly increased platelet counts but we haven't known why this happens or understood its relevance, if any, to disease progression," said senior author Anil Sood, M.D., professor in MD Anderson's Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology.

"Our collaborative study not only identified a mechanism that explains platelet count elevation, but also connects this state, called thrombocytosis, to the severity of ovarian cancer," Sood said. "This suggests drugs that interfere with coagulation might be a useful addition to conventional therapies."

Tumor makes IL-6, liver produces TPO, platelets abound, tumor grows

Drawing on clinical data from ovarian cancer patients and following up with mouse model experiments and a clinical trial, Sood and colleagues discovered:

High platelet counts often occur due to an underlying medical condition. Many people with thrombocytosis also have cancer, especially ovarian gastrointestinal, ovarian and lymphoma. In many cases, high platelet counts are considered to be an initial cancerous sign.

Risk

Some people might be at a significantly higher risk of developing high platelet levels within the blood. These people include those who have recently undergone any type of surgical procedure, and those who have iron-deficiency anemia.

* Ovarian cancers produce the inflammatory cytokine interleukin-6 (IL-6);
* Triggering creation of the platelet-production regulating hormone thrombopoietin (TPO) in the liver;
* Causing platelet counts to soar to more than 450,000 per cubic millimeter in the blood, the threshold for thrombocytosis, and
* Stimulating tumor growth and continuation of the cycle.

"Platelets may function as a fuel depot for tumors by providing them with growth factors," Sood said. They were found not only in the blood but also in the tumor's microenvironment, in the tumor bed, and in ascites, fluid build-up in the abdominal cavity common in ovarian cancer.

THE ROLE OF PLATELETS IN OVARIAN CARCINOMA Platelets represent one of the largest storage pools of angiogenic and oncogenic growth factors in the human body. The observation that thrombocytosis (platelet count >450,000/uL) occurs in patients with solid malignancies was made over 100 years ago. However, the clinical and biological implications as well as the underlying mechanism of paraneoplastic thrombocytosis associated with ovarian carcinoma remains unknown and were the focus of the current study.