How the Previstage™ GCC Colorectal Cancer Staging Test Works
Previstage™ GCC is the first test that uses genomic technologies to assess the stage of a colorectal cancer patient, which is known to be related to the risk of disease recurrence. The test measures the expression or absence of expression of a biomarker called guanylyl cyclase C (GCC or GUCY2C). GCC is expressed in cells lining the intestine from the duodenum to the rectum, and it is never found in normal tissue in other parts of the body. When GCC is detected in the lymph nodes removed during a colorectal cancer surgery, it is a strong indication of the presence of colorectal cancer metastases. The test is used for stage I and II patients, whose lymph nodes have been found free of cancer cells by the current microscopic staging method (called histopathology node-negative patients).
GCC or GUCY2C
GCC (or GUCY2C) is the first validated marker useful in detecting the presence or absence of colorectal cancer cells in the regional lymph nodes. The gene codes for a protein that is involved in multiple functions, including water transport, crypt morphology and suppression of tumorigenesis.
Dr. Scott Waldman, at Thomas Jefferson University, first identified the relation between GCC and colorectal cancer in the early 1990s. The U.S. National Institutes of Health provided grants totaling over $10 million to Dr. Waldman for two prospective 5-year multicenter studies on the GCC marker and its role in colorectal cancer. The first study was performed with over 400 enrolled patients from 9 different sites to identify the prognostic value of GCC. It was published in February 2009 in the Journal of the American Medical Association (Feb 18, 2009, Vol. 301, No. 7). The results of the study strongly demonstrate that testing of lymph nodes for GCC can more accurately predict the risk of stage I and II CRC patients having disease recurrence.
In the study, in a group of 257 stage I and II CRC patients, when GCC was considered independently from other factors, patients whose nodes were GCC positive were 4.7 times more likely to develop disease recurrence than those whose nodes were GCC negative. In fact, patients with GCC positive nodes had a risk of recurrence comparable to that of stage III CRC patients.
The article on this study is one of more than 50 publications documenting research on GCC. If you would like to learn more about GCC, consult our extensive library of publications at the DiagnoCure Oncology Laboratories website under Scientific Literature.
The benefits of genomic technologies
It is widely recognized that there is a clear link between metastases in the regional lymph nodes (staging) and the risk of recurrence. Currently, many stage I and II patients are understaged because there is an insufficient number of lymph nodes removed during the surgery, and hence available for examination, the histopathology review is done on only thin slices of each lymph node (very low volume of tissue), and the use of a microscope limits the detection to 1 cancer cell in a group of about 200 normal cells.
With genomic technologies, such as RT-PCR to detect the GCC mRNA expression in the lymph nodes, it is possible to overcome at least two of the weaknesses of the current histopathology method. With Previstage™ GCC, at least half of each lymph node provided is examined (usually 12 nodes or more), and the technology provides a detection capacity of 1 cancer cell in up to 10 million normal cells. Overall, the genomic technologies employed in Previstage™ GCC are 100,000 times more sensitive than the current histopathology method.
Treatment decision
The current guidelines for colon and rectal cancer treatment recommend: to not treat stage I patients and most stage II colorectal cancer patients; to consider for chemotherapy treatment stage II patients who are considered at high risk based on a number of factors; and to treat all medically fit stage III patients. The response to therapy in stage III patients demonstrates a clear benefit from adjuvant therapy. In stage II patients, the response varies widely probably because the factors used to identify the high risk patients are not sufficiently accurate. In comparison, Dr. Waldman’s studies concluded that patients who were GCC positive had a risk of recurrence comparable to stage III patients. Indeed, when considered separately from other risk assessment factors, GCC stood out as the best single predictor of risk of colorectal cancer recurrence.
Based on this evidence, at an educational session held during the 2009 Gastrointestinal Cancers Symposium (ASCO GI) which reviewed different markers for the prognosis of colorectal cancer patients, it was suggested that patients with GCC positive lymph nodes could be considered and treated as stage III patients.
There are a number of other factors that you and your doctor will take into account to decide if adjuvant therapy is appropriate for you. But with regard to your risk of recurrence, with Previstage™ GCC, you can be confident to rely on the most advanced genomic information.
The Previstage™ GCC Colorectal Cancer Staging Test is a laboratory-developed test. It was developed and its characteristics were determined by DiagnoCure Oncology Laboratories.
