It’s In The Blood: Houston Researcher Discovers New Test To Detect Abnormal Cancer Cells

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A Houston cancer researcher has discovered a new technique for identifying circulating abnormal cells in certain types of lung cancer patients.
Ruth Katz, M.D., professor in MD Anderson's Department of Pathology, is the first to use a technique called fluorescence in situ hybridization (FISH) to detect abnormal circulating cells that have aberrations found in non-small cell lung cancer. In a study published in the journal “Clinical Cancer Research” and announced on July 22, Katz and a team of University of Texas MD Anderson Cancer Center research scientists used the FISH analysis to detect significantly larger numbers of circulating abnormal cancer cells in the blood than previously existing detection methods. Previous detection methods used immunomagnetic beads attached to an antibody found on the surface of circulating cells that originate in an organ's epithelium. In contrast, FISH detects and quantifies abnormal cells by using dye-labeled DNA probes of cell chromosomes that cause cells with the targeted genetic abnormalities to light up when viewed under a fluorescent microscope.
If her breakthrough is validated by additional studies, then blood tests for circulating tumor cells could be used to diagnose lung cancer earlier, monitor response to therapy and detect residual disease in patients after treatment said Katz.  
When a person’s body is invaded by a malignant tumor, explained Katz, cells leave the tumor, invade the bloodstream and are carried by the blood to attack distant organs. And until now, the existing technology to detect these cancer cells in the blood has been “primitive”, she said.

“The existing tests were designed to look at epithelial cells,” said Katz. “They didn’t realize that the tumor cells that go into the blood are like stem cells. The stem-like cells keep on proliferating and differentiating. When these cells get ready to go into the bloodstream, they undergo a transition from being epithelial cells to mesenchymal cells--sort of like spindles instead of round-shaped. These slender spindle-like cells wriggle out of the tumor and express a marker.

“I’d been working in lung cancer, working with the probes we had patented. One was surfactant protein. We noticed epithelial cells in the sputum had these abnormalities. When we did this FISH test, I noticed the white blood cells had genetic abnormalities in the sputum. I had a hunch that if these cells were in the sputum, then these white blood cells would also probably be circulating in the blood.”

Katz obtained blood from patients with lung cancer and applied the same FISH probe used in the sputum to their blood.

“When I looked under the microscope, I had a eureka moment,” she said. “This was an end-stage cancer patient and there were so many of these cells that had the same abnormality in the blood. We found thousands of cells in the blood, 7,000-45,000 CACs (circulating genetically abnormal cells) per milliliter of blood. When I looked at the controls, they hardly had any CACs.”

Katz wrote a grant and got a patient study funded. Using 12 different biomarkers in 59 cases of non-small cell lung cancer and 24 controls (people without lung cancer), Katz found they all her cancer-patients showed very similar results. When the tumors were small, there were fewer circulating cells. But at stage four, there were huge numbers of circulating cells.

In essence, Katz found that abnormal cells were significantly associated with disease stage, with cells that contained certain abnormalities increasing significantly as cancer progressed from early to advanced stage disease.

Work is under way to develop a clinical test based on FISH.

Katz also noted that the machine she used to scan and image all these cells is an Israeli instrument made in Rehovot.

“It’s a bio-viewing instrument and actually it doesn’t even belong to me,” said Katz. “The CEO of the company, Alan Schwabel, is a religious guy. He came over to Houston and demonstrated the machine for us. He originally saw a role for the machine in bladder cancer. The machine is currently used extensively for urine cytology.

“Schwabel gave me the machine and we developed all these tests for circulating tumor cells. It’s been a great experience.

“Now we’re now looking at what happens when you remove the primary tumor. Do the circulating cells increase? If so, does that mean the cells have metastasized? And if they decrease, do the patients live longer?”

Of course, Katz’s research is a pilot study and must be validated by other, larger studies. But, said Katz, it was a thrilling, “even scary” feeling when she first realized her findings could achieve a potential breakthrough in the cancer detection field.

“It was difficult to get people to accept this at first because our approach is so novel and radical right now,” said Katz. “We’re in the era of personalized medicine and this test is very flexible. There are many different types of lung cancer. Every tumor shows different mutations. Because we are collecting and storing so many cells, if we have a unique genetic abnormality, we can use that abnormality to see what happens over time. You can really see how your patient is responding to various drugs, for example. And instead of using biopsies, you can look at the genetic composition in the blood to see if you can find a suitable drug that your patient will respond to.

“My late husband Mel died of lung cancer. He was diagnosed in 1999. And I got a contract to work on lung cancer a month before he was diagnosed. He wasn’t a smoker and he died 18 months later. About 20% of people with lung cancer don’t smoke. So after that, I decided to focus my research on lung cancer.

“Certainly this has been the best work I’ve ever done. When you make a discovery like this, it’s going to open a whole new area of research. Other researchers will follow similar principles for the other types of tumors. The only thing you need to learn is the genetic abnormalities for the cells of these tumors.

“In celebration and in gratitude and to thank HaShem for the giving me the koach (strength) and persistence to succeed, I invited Rabbi Y.Y. Rubinstein for an August 20-22 Shabbaton at the Meyerland Minyan. I’ve been blessed with a wonderful career and I’m grateful.”

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