While many oncologists agree that proteomics will play an increasingly important role in cancer research, a new screening test that utilizes the technology has been met in the United States with some caution. Some professionals question the interpretation and use of data for the lymphoma test, which has attracted interest from the consumer press. Professionals also wonder how to manage asymptomatic dogs that receive positive test results. While academics argue pros and cons—and efficacy—private practitioners are starting to field requests from clients for the new test.

Proteomics, the study of protein structure and its interaction with genome, has been used by the cancer research community, including veterinary scientists at the National Cancer Institute (NCI), for some time. NCI veterinarians are studying whether protein signatures can identify different disease states including cancer, said Chand Khanna, DVM, PhD, director of the NCI Comparative Oncology Program. “There has been great interest in this approach over the last several years,” he said.

Proteomics may not be new to the research scene, but a PetScreen test claiming to identify canine lymphoma became available last month and clients are asking for it. PetScreen professionals introduced the test at the 2006 North American Veterinary Conference, and an article in Gazette Magazine has generated client questions.  The company started accepting serum samples from the United States last month.

Two different tests, developed at Colorado State University (CSU) in 2002 identify lymphoma when cell pathologies are not clear. Developer Anne Avery, VMD, PhD, who works at CSU, emphasizes that these tests are not intended to screen for cancer. CSU offers a PCR test and flow cytometry when  doctors have aspirated nodes and do not obtain clear results. To date approximately 7,000 tests have been run for dogs and cats though cats represent a small number of patients, Avery said. She does not suggest the PCR test if the cell cytology shows cancer but said the flow cytometry differentiates between B and T lymphoma cells.

While the CSU test confirms a veterinarian’s suspicion of existing cancer, a screening test may pick up markers for cancer before the disease is present, which raises issues about treatment and how this information can be useful to clinicians and pet owners, according to sources.

In other words, what comes after a positive test for an asymptomatic dog?

In many cancers early diagnosis and treatment are helpful, Khana said, but additional studies are needed to know what steps should follow a positive screening test. "At this time we do not know whether a positive (lymphoma) dog should be treated or followed. It should not be assumed that early treatment of a dog [whose cancer] was detected with a screening test would be best,"  Khana said.

On the darker side of the treatment equation, some doctors fear that a positive test result for cancer would push pet owners in the direction of euthanizing a dog when presented with such a diagnosis. Studies that determine whether a positive test only occurs in dogs with lymphoma and not other diseases are needed, Khana said. He added that this critical information will allow doctors and owners to consider the impact of such a test.

"It will be very interesting to see whether this test can distinguish lymphoma from other cancers and other disease states," he said.

In the human world, screening tests for colon and prostate cancers are now common practice. Early treatment of these diseases has improved long-term outcome for patients, Khanna said. In comparison, cancers like lymphoma may not follow the stepwise progression model of those cancers.

In the United States, some doctors are wary of PetScreen’s research claims and a VIN thread illustrates concern about treatment steps if the test shows a positive result in an asymptomatic dog.

“There are a lot of doctors who are appalled that they are marketing this test,” said CSU’s Avery. In addition to questions about PetScreen’s data, which is not as extensive as some professionals would like, Avery says that because lymphoma is fast acting, doctors who conduct the $89 test (cost to veterinarians) could miss it even if a screening test were accurate.

Before using such a test, one veterinarian said he would like to know what the company’s false positive rate is for dogs of equal age that do not have lymphoma but do have infections or some kind of benign tumor.

Doctors who posted threads on VIN commented on a lack of clinical data for the test and that none of the proponents for it are veterinarians.

PetScreen professionals tested 92 normal dogs and 87 dogs with lymphoma, and explain that their test assesses the body’s reaction to cancer. Kevin Slater, PhD, chief executive officer, said multiple markers work because, “as a tumor develops in the body, it secretes a variety of different proteins into the blood. The body responds by changing the expression (and therefore circulating levels) of existing serum proteins,” which are picked up with proteomic technology.

“The multiple biomarker approach examines these changes in the blood by looking for the increased or reduced expression of a range of different proteins, which are identified by their molecular weight using a mass spectrometer. Since proteomics examines the up and down regulation of a range of different proteins, it is regarded as a better reflection of the body’s response to the tumor [instead of] looking for just a single biomarker,” Slater added. The test could be used at one-year intervals with senior dogs and at six-month intervals for dogs at high-risk for cancer, he said.

About 150 practices in the United States have registered with PetScreen, and about 3,500 practices in the United Kingdom have expressed interest or are using the test, which has an 84 percent sensitivity rating, Slater said. “We are seeing more [cancer] than we ever expected,” Slater said and added, “But it may not be an accurate reflection of cancer in the community,” because many doctors are using the test to confirm their diagnoses.

Cancer is the number one natural cause of death for cats and dogs, according to CSU, and lymphoma is one of the most common cancers found in dogs. It can grow quickly and frequently dogs do not show signs of illness, which is why testing – and regular check-ups – are so important, say professionals.