By Doug Macron
Asuragen said this week that it has established a number of collaborations to develop a new version of its microRNA-based pancreatic diagnostic that will use fine-needle aspirate biopsies, rather than samples obtained from formalin-fixed, paraffin-embedded tissues.
The test is expected to be available in the second half of this year through Asuragen's Clinical Laboratory Improvement Amendments-certified lab.
In early 2008, Asuragen began marketing an miRNA-based diagnostic assay designed to differentiate pancreatitis from pancreatic ductal adenocarcinoma, a move that made the company the first to commercialize a test based on the small, non-coding RNAs (see RNAi News, 4/24/2008).
"Differentiation between a benign condition of chronic pancreatitis and pancreatic carcinoma is often difficult, as both conditions may present with the similar symptoms … and are not mutually exclusive," according to the company.
"Additionally, chronic pancreatitis shares many of the histopathological and imaging features of pancreatic carcinoma both microscopically and during preoperative imaging studies," it adds on its website. "Inaccurate diagnosis can lead to major surgery for benign disease or delay of surgery for a potentially curable lesion."
Addressing this issue, Asuragen's FFPE test analyzes the raw expression difference of two miRNAs: miR-196a and miR-217. "This miRNA signature is a balanced set wherein, one gene product is expected to be up-regulated in pancreatic ductal adenocarcinoma, miR-196a, while the other is expected to be down-regulated, miR-217, as compared to normal pancreas tissue and chronic pancreatitis tissue," the company said, citing data that company researchers published in 2007.
While studies have shown this test to have a sensitivity of 95.2 percent and a specificity of 94.9 percent, it requires FFPE samples, which can require surgery to obtain. As such, Asuragen has begun exploring whether fine-needle aspirate samples could be used to measure the expression levels of miR-196a and miR-217.
Last year, company researchers published data showing that miRNAs could be detected in FNA biopsies of pancreatic ductal adenocarcinoma and could accurately differentiate malignant from benign pancreatic tissues.
These findings demonstrated that "profiles of miRNA production can aid in the pathologic evaluation of suspicious cases and may become a valuable asset in obtaining a definitive diagnosis of" pancreatic ductal adenocarcinoma, the paper's authors wrote.
Still, "additional studies are needed to retrospectively analyze archived formalin-fixed, paraffin-embedded samples and prospectively evaluate the utility of the use of miR-196a and miR-217 in conjunction with the [FNA] procedure to complement the current standard histologic and cytologic diagnosis of pancreatic diseases," they added in the paper.
To meet this goal, Asuragen this week announced that it has begun collaborating with the University of Pittsburgh Medical Center, Brigham and Women's Hospital, the H Lee Moffitt Cancer Center, Dartmouth's Hitchcock Medical Center, and the University of Sherbrooke to clinically evaluate a miRNA test based on FNA biopsies to differentiate pancreatic adenocarcinoma from chronic pancreatitis and other such non-cancerous conditions.
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"These research collaborations will help Asuragen evaluate the potential clinical utility and diagnostic performance of miRNAs for diagnosing pancreatic cancer using FNA biopsies, which can be obtained less invasively and may allow patients to avoid unnecessary surgery," the company said.
In setting its sights on a next-generation version of its existing pancreatic cancer test that still uses tissue samples, Asuragen has taken a more cautious, but apparently more realistic path toward the development of new miRNA-based diagnostics than some of its peers, which have begun eyeing blood-based tests in earnest.
For example, early last year Rosetta Genomics said that it had shifted its focus away from miRNA diagnostics onto miRNA screens that would measure expression levels of the RNAs in serum, with an initial focus on a colon cancer test.
Meanwhile, Exiqon has been working on an miRNA-based colon cancer diagnostic that would be based on a blood sample, and said last summer that results from a collaboration to develop the test would be ready in the first quarter of this year, although a timeline for the product's market introduction was not forthcoming (see RNAi News, 8/27/2009).
However, the analysis of miRNAs from blood samples appears to be a trickier proposition than expected. At the end of 2009, Rosetta backtracked, stating that it had scaled back work on its colon cancer screen after running into "technical obstacles" that stymied the consistent measurement of miRNA biomarkers in serum (see RNAi News, 12/31/2009).
Around the same time, University of Massachusetts Medical School researcher and miRNA pioneer Victor Ambros told RNAi News that while miRNAs in the blood are a promising area of research, they are "mysterious" and their meaning "still pretty obscure."
"We … need to learn more about the biological meaning of these circulating microRNAs," Ambros said. "What is their physical form, where do they come from, how are they produced, what is the range of particles and their sources and their destinations that are present in circulation? It's amazingly uncharacterized at the moment."
And while Exiqon has yet to release its findings, Rosetta's troubles and Ambros' insights suggest that a blood-based miRNA test may not quite be ready for prime time.