Molecular staging or genomic profiling holds promise in predicting the long-term outcome of an individual patient based on the gene expression profile of their cancer at diagnosis. Researchers have shown that a gene signature test ? called ColoPrint ? that analyzes the expression of 18 genes can identify the risk of recurrence in colorectal cancer patients with localized, stage II disease.

Such a gene signature test could have important implications for treatment decisions: although most stage II colorectal cancer patients do well with surgery alone, about 20% of these patients experience cancer recurrences and could benefit from adjuvant chemotherapy to reduce this risk. The results of the study were presented during the eighth annual Gastrointestinal Cancers Symposium, which will be held January 20-22, 2011, at The Moscone West Building in San Francisco.

?We are extremely encouraged by what these results may mean for colorectal cancer patients,? said lead author and surgeon Robert Rosenberg, MD, an assistant professor at the University Hospital of the Technical University in Munich, Germany.

?While several research groups have developed prognostic multi-gene tests that vary in technology, number of genes and method of analysis, ColoPrint is among the first test for colon cancer patients. It was validated in two independent patient series and is assessed in a prospective trial. Gene signature tests are already routinely used to improve breast cancer treatment, and we are well on our way to develop a similar model to guide treatment of stage II colorectal cancer.?

According to Dr. Rosenberg, researchers have long sought better ways to identify stage II patients at risk for recurrence. Clinical factors ? tumor stage, number of assessed lymph nodes, and an obstruction or perforation at diagnosis ? are among those carefully considered in identifying high-risk patients and making decisions on treatment options. Yet, these clinical factors have proven inadequate to make reliable prognoses.

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In this study, investigators examined tumor tissue removed from 233 patients who underwent surgical resection for stage II or stage III colorectal cancer from 1987 to 2003 at the University Hospital in Munich. Using ColoPrint (Agendia), a microarray-based diagnostic test, they analyzed tumors for the expression of 18 colon cancer recurrence-specific genes gleaned from the human genome. With this technology, the resulting expression profile, or fingerprint, of the tumor was compared to the activity of these genes in a reference population of hundreds of ?normal? genes simultaneously to determine a score that indicates high or low recurrence risk. Developed on the entire genome, ColoPrint, Dr. Rosenberg noted, enables a clear result of low or high recurrence risk and helps differentiate the test from other assays.

In the 135 stage II patients, the ColoPrint results were compared to relevant clinical factors, such as age, gender, localization of tumor, grade, number of assessed lymph nodes, and tumor stage.

Investigators found ColoPrint was effective at identifying those patients at higher risk of cancer recurrence. ColoPrint identified 73 percent of the stage II patients as low-risk, and just 5 percent of this group experienced a cancer recurrence within five years or more. ColoPrint identified the remaining 27% of stage II patients as high-risk, and 20% of these patients experienced a recurrence, with a median follow-up of 97 months.

?The ColoPrint gene expression test was the only significant factor that predicted the development of distant metastasis in our patient series,? Dr. Rosenberg said. ?In this validation study, the performance of ColoPrint seemed to be independent of known clinical factors. ColoPrint was able to predict outcome in stage II patients, and this facilitates the identification of patients who may be safely managed without chemotherapy.?

The value of the gene signature test in risk assessment for recurrence currently is being prospectively compared to clinical risk factors in PARSC (Prospective Analysis of Risk Stratification using ColoPrint), an international, multi-center, clinical study of patients with stage II colon cancer. ColoPrint is also being evaluated for stage III colorectal cancer.

?If the results from the ongoing studies validate our findings, we will be able to use ColoPrint in routine clinical practice as a commercially available assay,? Dr. Rosenberg said. ?Further goals are to combine results of the gene signature test with clinical parameters to further improve patient stratification and to offer individualized therapy options to our patients.?

ColoPrint is currently in the validation stage and scheduled to be launched in 2012.

For more information:
Rosenberg, M. Maak, I. Simon, U. Nitsche, T. Schuster, B. Kuenzli, et al. Independent validation of a prognostic genomic profile (ColoPrint) for stage II colon cancer (CC) patients. Abstract #358

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