DENVER—The acquisition, storage, and handling of high-quality human biospecimens has been a major roadblock in the development of molecular biomarkers for cancer diagnostics and for designing targeted anticancer drugs.
Speaking here at the AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development, though, Kelly J. Bethel, MD, a practicing hematopathologist at Scripps Clinic and senior clinical investigator at Scripps Research Institute, suggested that if investigators want to get their cell line research transferred over to human biotissue, they should get to know their local pathologist.
“Befriend your pathologist,” Dr. Bethel said. “In any hospital setting the pathologists are the people who control the tissue. We sit on the committees, and we set the rules for how tissue is handled.”
She said researchers who will need human biospecimens at some point in their project should involve the institution's pathologists early on, to see what samples the pathologist might give the researcher access to and in what form.
“Do you want them unfixed? Do you want them frozen? Do you want them in single cell suspensions? Do you want a chunk? Those are the kinds of conversations that you need to be having very early on in the concept phase of your projects or you're not going to be able to make as much progress.”
There is often very little tissue from a procedure to give away, Dr. Bethel said. “It's hard to get enough material to get a diagnosis with the exception of a big organ resection. Usually we're struggling with little, tiny pieces and the oncologist is yelling in our ear, ‘Is it cancer, is it cancer?'
“And we've got three cells that we're frantically trying to work on, and along comes a researcher who says, ‘Hey! Can I have the rest of that?'
“You're disinclined to be too cheerful about that,” she said.
The diagnostic adequacy rate of sampling procedures is related to the type of biopsy, Dr. Bethel explained. From a resection there is usually plenty of tissue to share, and with excisional biopsies there is sometimes a little bit of margin around the tumor—“but sometimes there's not, depending on the tumor and the organ.”
From an incisional biopsy, there is usually “just enough” taken to make the diagnosis.
And from fine needle and core needle biopsies, “you take what you can get, and there surely isn't going to be any left over for research,” she said.
“The plain truth in all of these cases is that research samples are considered second priority after adequate diagnostic material is obtained.”
‘Make It Worth Their While'
Dr. Bethel told researchers here to “befriend a nearby pathologist and fund their time.”
Ideally, she said, the researcher will include funding for the pathologists' work in the grant proposal. But that opens the question of how much does it really cost to find, prepare, and properly ship a specimen. It may be that the question has never been asked, and a thorough calculation could be a shock to the researcher and pathologist alike, she said.
Sharing biospecimens with researchers can already be an institutional challenge even if funding is not involved. For example, Dr. Bethel said, she might get a memo from the hospital CEO noting that the pathology lab's productivity was a bit low on a certain day, and suggesting that she is perhaps spending too much time searching for and preparing biospecimens for researchers again, “and that's not really in the interest of our bottom line.”
“If researchers could fund pathologists' time, that would get the hospital executives off our backs, and we could think clearly about this and help you design your experiments,” she said.
But the first stop in all this is to involve the pathologist in the experimental design—“We know what you're likely to get with various sampling strategies,” she said. “This is our life.”