About The Gazette Search Back Issues Contact Us    
The newspaper of The Johns Hopkins University July 23, 2007 | Vol. 36 No. 40
Colon cancer proteins show promise for blood test

By Vanessa Wasta
Johns Hopkins Medicine

Searching for less invasive screening tests for cancer, Johns Hopkins scientists have discovered proteins present in blood that accurately identify colon cancer and precancerous polyps.

Initial studies of the proteins CCSA-3 and CCSA-4 suggest they could be used to develop a blood test to identify at-risk individuals.

"The reality is that many people are not getting regular screening colonoscopies, so ideally we'd like to identify those with some molecular fingerprint for the disease and really need them," said cancer researcher Robert Getzenberg, a professor of urology and director of research at Johns Hopkins' Brady Urological Institute."

Current screening guidelines for healthy people call for a baseline colonoscopy — the insertion of a flexible optical-scanning scope through the rectum into the colon, preceded by colonic cleansing, fasting and heavy sedation — at age 50, followed by rescreening at least every five to 10 years. Colonoscopy is not foolproof; cancers can develop between screenings.

First discovered by Getzenberg and colleagues at the University of Pittsburgh through a protein scan, the two blood-dwelling proteins are thought to be remnants of cellular debris cast off from dead cancer cells. Although the proteins' roles are not entirely clear, the Johns Hopkins scientists say they are part of the scaffolding that supports structures within a cell's control center, the nucleus.

Alteration of such nuclear scaffolding is a hallmark of cancer cells that is easily detectable under the microscope as a misshapen and discolored nucleus. That fact led Getzenberg to the notion that "there must be something at the molecular level that would form a molecular flag for cancer via a blood test."

To find the flag, Getzenberg's team drew blood samples from 107 apparently healthy individuals the day before their scheduled colonoscopies, and from 28 colorectal cancer patients.

Using a particular concentration of scaffold-proteins as a marker for disease, the Johns Hopkins team — which did not know the colonoscopy results in advance — was 100 percent accurate in identifying the 28 existing cancers. Using the same protein markers, investigators also correctly identified 51 of 53 individuals (96.2 percent) with normal colons and 14 of 18 people (77.8 percent) with advanced precancerous polyps, which Getzenberg says are the most important to detect through routine screening.

When researchers combined samples, they correctly identified 42 of 46 (91.3 percent) containing both cancers and advanced precancerous polyps. Protein levels were accurate in correctly assessing additional blood samples from 125 people with benign conditions and other cancers.

"These proteins seem very good at separating normal samples from cancerous ones and identifying other groups with precancers at high risk for disease as well," Getzenberg said. Results are published in the June 15 issue of Cancer Research.

The researchers are planning larger studies at several hospitals over the next several months. It may take several years to complete the full range of testing.

Getzenberg says that storing and processing the samples are among the major hurdles in biomarker development, a field that spans ongoing research on many cancers and various body fluids. "It is difficult to get many facilities to adhere to precise storage and processing conditions important for keeping proteins stable," he said. "Different conditions could create incorrect results." Researchers also differ in the type of biomarkers they seek, with some, like Getzenberg, looking for proteins, and others searching for DNA components.

Getzenberg and the University of Pittsburgh hold a patent for the technology described above, which is licensed to Onconome. Funding for the study described in the article was provided by Onconome and the National Cancer Institute. Under a licensing agreement between Onconome and the University of Pittsburgh, Getzenberg is entitled to a share of royalties received by the university on sales of products described in this article. Getzenberg also is a paid consultant to Onconome, which has a licensing agreement with The Johns Hopkins University covering CCSA-3 and -4 related technologies. The terms of this arrangement are being managed by Johns Hopkins in accordance with its conflict-of-interest policies.

Additional authors are Eddy S. Leman, Grant W. Cannon, Lori J. Sokoll and Daniel W. Chan, all of Johns Hopkins; and Robert E. Schoen and Joel L. Weissfeld, of the University of Pittsburgh Cancer Institute.


Related Web sites

Kimmel Cancer Center at Johns Hopkins
Brady Urological Institute at Johns Hopkins


The Gazette | The Johns Hopkins University | Suite 540 | 901 S. Bond St. | Baltimore, MD 21231 | 443-287-9900 |