By Doug Macron
Asuragen this week announced the launch of a new version of its pancreatic cancer diagnostic miRInform Pancreas, which uses a broad panel of microRNAs from fine needle aspirate specimens and which the company said marks the culmination of years' worth of validation work.
The test is specifically designed to help physicians differentiate between pancreatic ductal adenocarcinoma and pancreatitis, conditions the company said share certain symptoms and are not mutually exclusive. “Additionally, chronic pancreatitis specimens share many of the histopathological and imaging features of pancreatic cancer, both microscopically and during pre-operative imaging studies,” Asuragen added.
Now with two types of the test commercialized — the FNA version and another that uses formalin-fixed, paraffin-embedded specimens — Asuragen has set its sights on a third miRInform Pancreas diagnostic based on cystic fluid samples, according to a company official.
In 2008, Asuragen became the first to market with an miRNA diagnostic when it launched the first-generation miRInform Pancreas test, which analyzes the expression of two miRNAs, miR-196a and miR-217, in formalin-fixed, paraffin-embedded specimens (GSN 5/2/2008).
However, the company has long had its eye on an FNA-based approach for the test, recognizing that the FFPE diagnostic has, in the words of Asuragen President Rollie Carlson, “limited application” (GSN 4/21/2011).
As early as 2008, the company was generating data showing that miR-196a and miR-217 could be detected in FNA biopsies of pancreatic ductal adenocarcinoma and could accurately differentiate malignant from benign pancreatic tissues.
In a paper published that year, Asuragen researchers reported that miR-196a and miR-217 could be detected in FNA biopsies of pancreatic ductal adenocarcinoma and could accurately differentiate malignant from benign pancreatic tissues.
However, they cautioned that "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.”
To do so, Asuragen formed research alliances in 2010 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 different miRNAs from FNA biopsies to see if they could help differentiate pancreatic adenocarcinoma from non-cancerous pancreatic conditions (GSN 2/4/2010).
By late 2011, Asuragen had positive data in hand, reporting at the American Pancreatic Association annual meeting that it and its collaborators had identified a signature of seven proprietary miRNAs — miR-130b, miR-135b, miR-148a, miR-196a, miR-375, miR-96 and miR-24 — that could be obtained from FNA specimens to make such a determination (GSN 11/10/2011).
According to that presentation, they used a panel of 95 FFPE samples to develop the miRNA signature, then tested its ability to predict PDAC status on an independent set of 186 FNA samples.
Based on the miRNAs' expression patterns, Asuragen was able to diagnose PDAC with 92.5 percent accuracy compared to 80.2 percent for FNA cytology alone. The firm was also able to characterize samples with "indeterminate or suspicious FNA cytology" with an overall accuracy of about 75 percent, it reported.
“These results demonstrate the value of the miRInform Pancreas test in resolving indeterminate cases and reducing false negatives resulting from FNA cytology, which promises to improve the diagnosis of PDAC and permit the selection of the most appropriate treatment for these patients,” Asuragen said this week.
On its website, Asuragen noted that the miRInform Pancreas FNA test has only been validated for use with solid masses, not cystic fluid. But the company is already taking steps to change that.
At last year's American Pancreatic Association meeting, the company also reported early data suggesting that a panel of nine miRNAs could be used to identify pancreatic cysts that are likely to become cancerous.
In collaboration with the Johns Hopkins University School of Medicine, Asuragen evaluated RNA from microdissected formalin-fixed paraffin-embedded tissue from intraductal papillary mucinous neoplasms and from cyst fluid samples.
The expression of 754 miRNAs was measured using 23 FFPE samples and 15 cyst fluid samples, while a separate verification set comprised 38 tissue and 50 cyst fluid samples. In a blinded validation study of pancreatic cyst fluid specimens, a nine-miRNA model had 89 percent sensitivity and 100 percent specificity in distinguishing low-risk cysts from high-risk cysts to inform treatment.
The group found 26 and 37 differentially expressed miRNAs between low-grade and high-grade IPMNs, respectively, with four overlapping. Nineteen of the miRNAs selected were able to differentiate between high-grade and low-grade IPMNs, as well as identify other uncommon cysts such as solid pseudopapillary neoplasms and cystic neuroendocrine tumors.
The investigators were able to winnow down this group of miRNAs to nine, which could determine appropriate treatment of either surgical resection or conservative watchful waiting with an accuracy of 90 percent and 100 percent, respectively.
This week, Carlson told Gene Silencing News that the company is currently validating this nine-miRNA panel. Depending on how quickly it can accrue appropriate specimens for validation, Asuragen could launch a cystic fluid-based version of miRInform Pancreas before the end of 2012, he noted.
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