CD24 FOR COLORECTAL CANCER AND PAM4 FOR PANCREATIC CANCER DETECTION

January 21, 2010 (Orlando, Florida) — Investigators reported promising results from 2 blood tests that could allow for the early detection of colorectal and pancreatic cancers here at the 2010 Gastrointestinal Cancers Symposium.

The annual meeting is cosponsored by the American Gastroenterological Association, the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

A team from Israel reported that a simple test for blood levels of the CD24 protein is more than 90% sensitive and specific for detecting colorectal cancer, and more than 80% accurate at identifying adenomas.

The CD24 protein is a cell-surface protein and P-selectin ligand that is involved in cell adhesion and metastasis, and has previously been associated with colorectal cancer (CRC) (Gastroenterology. 2006;131:630-639). The aim of the current study was to evaluate CD24 protein expression in peripheral blood lymphocytes (PBLs) from normal subjects and from subjects with CRC or adenomas.

"There is currently no serum-based test that is of sufficient sensitivity or specificity to be useful," said Sarah Kraus, PhD, who presented the findings. Dr. Kraus heads the research laboratory at Tel Aviv Souraski Medical Center in Israel.

"We found that serum CD24 is elevated in the majority of patients with CRC or adenomas. We believe a simple blood test that measures the level of CD24 in PBLs can successfully distinguish healthy subjects from those with neoplasia, and may serve as a biomarker for early detection and surveillance of CRC," she said at a press briefing.

In the study, 150 consecutive subjects underwent colonoscopy. PBLs were isolated from serum samples, and protein extracts were analyzed for these subjects. The same procedure was followed in a second validation trial of 73 consecutive subjects, for whom results were presented here.

CD24 protein levels proved to be sensitive and specific for distinguishing patients with no abnormal findings on colonoscopy from those with CRC and adenoma, Dr. Kraus reported. The protein levels were approximately 2000 OD/mm² in normal subjects and 12,000 OD/mm² in patients with either adenomas or cancer.

The sensitivity for the detection of CRC was 92.3% and for adenomas was 75.0%. The specificity for each, respectively, was 83.8% and 89.2%. In the analysis of both groups combined, sensitivity was 78.4% and specificity was 86.8%.

Pancreatic Cancer Also Detected Early

In another study, an immunoassay showed promise for detecting early-stage pancreatic cancer with a high degree of accuracy. The assay identifies and quantifies serum PAM4 protein, an antigen that is present in nearly 90% of pancreatic cancers but is not typically observed in association with benign lesions or other malignancies.

"We found that the PAM4 protein is quite accurate at identifying patients with pancreatic cancer and, if validated in larger studies, would be a promising tool for detecting the disease when our potentially curative procedures have a better chance for a good outcome," said David V. Gold, PhD, from the Garden State Cancer Center in Belleville, New Jersey. The study was done in collaboration with Johns Hopkins Medical Institutes in Baltimore, Maryland.

The PAM4 monoclonal antibody, also known as clivatuzumab, identifies a unique biomarker with a high specificity for a mucin glycoprotein expressed by pancreatic adenocarcinoma. The protein is not detectable in normal pancreatic cells or in cells of patients with chronic pancreatitis, a condition that can be otherwise hard to distinguish from cancer.

"The PAM4 test has the ability to detect PAM4 antigen in the blood, a protein produced by the tumor that may act as a marker, not only for diagnosis but for targeted therapies," Dr. Gold told media representatives.

The PAM4 enzyme immunoassay was performed on 68 patients who had undergone pancreatic surgery and 19 healthy controls. Its overall sensitivity for detecting pancreatic cancer was 81%; it has 62% sensitivity for detecting stage I pancreatic cancer, 86% sensitivity for stage II disease, and 91% sensitivity for stage III/IV disease, Dr. Gold reported.

"The PAM4 assay detected the overwhelming majority of patients with early-stage pancreatic cancer and 91% with late-stage disease," he said. "PAM4 is very specific for pancreatic cancer. It indicates a high possibility that a patient will have pancreatic cancer."

Dr. Gold predicted that the test will not be used for universal screening, but would best be applied to individuals suspected of having cancer or deemed to be at high risk for pancreatic cancer. This includes people with long-term chronic pancreatitis and diabetes, heavy smokers and drinkers, and those with a family history of hereditary forms of pancreatitis or pancreatic cancer, he said.

Both investigators indicated their assays are being further developed and might be clinically applicable within 2 to 3 years.

Robert Sticca, MD, professor of surgery at North Dakota School of Medicine and Health Sciences in Grand Forks, who moderated the press briefing, explained that these investigations are part of a larger research effort to develop tests that are highly accurate for detecting gastrointestinal cancers at an early stage.

"For pancreatic cancer, the medical profession has long struggled with the treatment of this disease, and these are very exciting data. If we had a test to detect it earlier, we would certainly do much better at managing it and preventing deaths," he said.

"The colorectal data are also preliminary, but if this test can be validated, it should be very beneficial in preventing deaths from this very common form of cancer."

The researchers have disclosed no relevant financial relationships.

2010 Gastrointestinal Cancers Symposium: Abstracts OP162 and 135. Presented January 22-24, 2010.