ORLANDO—Accurate detection of micrometastases in the lymph nodes of colorectal cancer patients appears possible with an emerging quantitative RT-PCR assay being developed by DiagnoCure Oncology Laboratories (West Chester, Pennsylvania), according to an interview with investigators at the 2008 Gastrointestinal Cancers Symposium. Data from a large prospective NIH-sponsored trial are expected to be reported at ASCO 2008.
The assay, Previstage GCC Colorectal Staging Test, identifies the expression of the gene for guanylyl cyclase C (GCC). GCC is an intestinal tumor suppressor and the receptor for bacterial diarrheagenic enterotoxins that is a constituent of cells lining the colon and is found no where else in the body under normal conditions (see Figure). The identification of GCC mRNA outside of the intestine (such as in the lymph nodes) is a highly sensitive, early indication of occult colorectal cancer metastasis, according to research led by Scott Waldman, MD, PhD, of Thomas Jefferson University.
Timothy Holzer, PhD, vice president of R&D and production for DiagnoCure, told ONI, “When there is evidence that a colon cell has left the intestine and exists anywhere else in the body, we know that is a very dangerous thing.”
About 30% of patients who are node negative by histopathology will have recurrences, suggesting that occult disease in the lymph nodes was missed by conventional histopathological techniques. The qRT-PCR technology used in identifying GCC is a vast improvement, Dr. Holzer noted.
RT-PCR is up to 100,000 times more sensitive than traditional histopathology in detecting occult metastases, as it can detect 1 cancer cell in up to 10 million normal cells vs 1 in 200 by traditional assays. Dr. Holzer said his company believes that the Previstage GCC test will be a reliable prognostic marker of micrometastases and thus will be a far more accurate means of staging colorectal cancer patients.
“Later this year, we will present the results of Dr. Waldman’s 5-year study,” he said. While he would not reveal any data, he said the interim findings suggest “the test very accurately predicts the risk of recurrence.” Patients who were negative by both histopathology and GCC had a very low risk of recurrence, he said. Those who were histopathology negative but GCC positive had a worse prognosis—“and this is a large proportion of patients,” he said. “Many patients apparently are staged incorrectly by histopathology.”
‘Looking forward to more data’
George Chang, MD, of M.D. Anderson Cancer Center, said he was impressed by what he heard of the test at the meeting. Dr. Chang has conducted seminal research in the area of lymph node counts and colorectal cancer (see article above).
“The real advantage comes from the fact that H&E is an imperfect test for lymph node metastasis. If a patient is negative by H&E, this does not mean there are no tumor cells in the lymph nodes,” Dr. Chang said. Immunohistochemistry with cytokeratin is also ineffective, according to sentinel node data, he added.
“The new RT-PCR assay would give us so much more resolution than the other tests. I am looking forward to seeing more data,” Dr. Chang said.