The researchers identified new markers related to the tumor microenvironment that define which patients are at greatest risk of dying from prostate cancer, said Dr. Gustavo Ayala, professor of immunology and pathology and urology at BCM. He and his colleagues describe their findings in a study to be presented at the American Society of Clinical Oncology in Chicago June 5.
Ayala and his colleagues tested tissue from 640 patients for evidence of a host of biomarkers. It validated the prognostic value of the Gleason score, commonly used to “grade” the virulence of prostate cancers.
They also confirmed that the risk of death from prostate cancer is greater when it has invaded nearby tissue called the seminal vesicles.
They also identified new biomarkers from the tumor microenvironment, the tissue that surrounds the cancer.
Reactive stroma grading
One is called reactive stroma grading, which is actually a measurement of how the host responds to the cancer. The other is perineural invasion diameter, a measurement of the diameter of the tumor around the nerve, an indication of how successfully tumor and nerve have interacted, said Ayala.
“We knew that cancers with no stroma are aggressive,” said Ayala. “Now we know that cancers with a lot of stroma are bad.”
Reactive stroma is the body’s response to injury, preparing it to close the wound with new tissue that surrounds an organ (also known as the epithelium).
Cancer is like a wound, so there is a constant wound or production of new cancerous tissue, said Dr. David Rowley, professor of molecular and cellular biology at BCM and a member of the research team.
“Cancer loves to have a helper in the form of reactive stroma,” said Ayala, also a member of the NCI-designated Dan L. Duncan Cancer Center at BCM.
“It provides all the factors the tumor needs for growth.”
We know tumors with increased reactive stroma become more aggressive and increase the likelihood of death, Ayala said.
Another valuable predictor
Additionally, the team found perineural invasion diameter percentage, or the growth of a tumor along the nerve, is a valuable predictor.
“We know that cancer wraps around the nerve, that it grows more in the presence of the nerve,” said Ayala. “Why? Because the nerves never die unlike other cells in our body – skin, mouth, etc.”
In medicine, biomarkers can reflect the presence and, sometimes, the severity of a disease.
Knowing a patient’s risk of dying from prostate cancer can help the patient and doctor decide the most effective approach to treatment and follow up, said Ayala. “We know tumors with increased reactive stroma become more aggressive and increase the likelihood of death.
Ayala’s previous work has shown that interaction between the cancers and nerves are among the most significant to determine true tumor aggressiveness.
“These results suggest that the tumor microenvironment is critical in the determination of patients who will die of prostate cancer,” said the authors.
This predictability, the researchers said, might lie in the study of the host or microenvironment and its response, not the cancer.
Others involved in the work include Drs. Brian J. Miles, Rile Li, Michael Ittmann, Dov Kadmon, Thomas Wheeler, David Rowley and Anna Frolov, all of BCM; Dr. Peter Scardino, Memorial Sloan-Kettering Cancer Center, and Dr. Christian Freund, The Methodist Hospital.
Support for this work came from the Helis foundation and the National Cancer Institute.
The study abstract is currently available online.