February 2013, Vol 2, No 1

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In Colon Cancer, Genomic Classifiers Aid in Prognosis

Caroline Helwick


Genomic classifiers – in particular, ColoPrint and MSI-Print, and best when combined – can identify high-risk subsets among surgically resected stage II and stage III colon cancer patients, MD Anderson Cancer Center researchers reported at the 2013 GI Cancers Symposium.

“The combination of ColoPrint and MSI-Print improves the prognostic accuracy in stage II and stage III patients and may help identify patients at higher risk who are more likely to benefit from additional treatment,” said Scott Kopetz, MD, PhD, lead author.

“Although the benefit of chemotherapy in stage II and III colon cancer patients is significant, many patients might not need adjuvant chemotherapy because they have a good prognosis even without additional treatment,” he added.

ColoPrint is a gene expression classifier that distinguishes patients with low or high risk of disease recurrence. It was developed using whole genome expression data and has been validated in public data sets, independent European patient cohorts, and technical studies. The 64-gene MSI-signature, MSI-Print, is a genomic signature for the detection of colorectal cancer patients with microsatellite instability phenotype and high mutation frequency and is linked to deficient mismatch repair (dMMR). A dMMR system is present in 10% to 20% of patients with sporadic colon cancer and is associated with a favorable prognosis in early-stage disease.

The population included 96 stage II patients and 94 stage III patients followed a median of 64 months. In this cohort, ColoPrint was prognostic for recurrence. The test classified 56% of stage II and stage III patients as being at low risk for recurrence. The 3-year recurrence-free survival (RFS) was 90.6% for low-risk and 78.4% for high-risk patients, with a hazard ratio of 2.33 (P=.012). In univariate and multivariate analyses,
ColoPrint and stage (stage III vs stage II) were the only significant factors to predict outcome.

The MSI-Print classified 24.6% of patients as MSI-high (which is prognostically favorable), and most of these (81%) were low risk by ColoPrint.
“Patients who were ColoPrint low risk and MSI-
high by signature had the best outcome, with a 3-year RFS of 95%, while patients with ColoPrint high risk had a worse outcome independently of the MSI status,” Kopetz reported.

One-fourth of patients were characterized as “MSI-Print-high,” which was previously defined to incorporate both MSI-high tumors and additional tumors that share similar gene expression features. In this population, MSI-Print did not provide independent prognostic ability but did provide additional information when combined with ColoPrint.

Low-risk ColoPrint patients had a good outcome independent of stage or chemotherapy treatment. RFS at 3 years was 90.1% for treated patients and 91.4% for untreated patients. ColoPrint high-risk patients treated with adjuvant chemotherapy had a 3-year RFS of 84%, compared with 70.1% for untreated patients (P=.037).

Kopetz added that ColoPrint is independent of traditional American Society of Clinical Oncology (ASCO) high-risk features, with 50% of cases discordant based on the presence or absence of high-risk features and ColoPrint results. For example, among patients classified as high risk by ASCO clinical features, only 34% were high risk by ColoPrint and 41% were low risk. Among those at low risk by ASCO clinical features, 16% were low risk by ColoPrint and 9% were high risk.

The genomic classifiers, therefore, add information above and beyond that obtained through conventional means, he said.

Uncategorized - February 20, 2013

Mayo Clinic Researchers Propose Screening Algorithm for HER2 in Esophageal Cancer

The preferred screening test for HER2 status in surgical esophageal adenocarcinoma specimens is immunohistochemistry (IHC), with fluorescence in situ hybridization (FISH) restricted to cases with an indeterminate (2+) IHC score, according to investigators from the Mayo Clinic, Rochester, MN, who proposed a testing algorithm at the 2013 GI Cancers Symposium. [ Read More ]

Interview with the Innovators - February 20, 2013

Next-Generation Sequencing:

An Interview with Michael J. Pellini, MD, of Foundation Medicine

As the molecular drivers of cancer are better understood and targeted therapies are developed against those drivers, there is a growing need to perform comprehensive molecular analysis of tumors to determine the optimal treatment strategy for each patient. To this end, Foundation Medicine was founded in April 2010 by leaders [ Read More ]