GRANTEE: Aatur Singhi, MD, PhD
University of Pittsburgh
Research Project: Diagnostic Markers of Malignant Transformation in Mucinous Pancreatic Cysts
Award: 2016 Pancreatic Cancer Action Network Translational Research Grant
Award Period: July 1, 2016 – June 30, 2018
Dr. Singhi is an assistant professor of pathology at the University of Pittsburgh Medical Center (UPMC) and within the Division of Gastrointestinal Pathology Center of Excellence. Dr. Singhi graduated from Northwestern University with a BS degree in chemistry and then earned his PhD in molecular genetics from the University of Illinois at Chicago. He received his MD from Case Western Reserve University School of Medicine, followed by residency and fellowship in pathology at Johns Hopkins Hospital. There, he received subspecialty training in pancreatobiliary and gastrointestinal tract pathology. Dr. Singhi’s research interests revolve around the pathology and molecular genetics of pancreatic cancer and precancerous abnormalities, with an emphasis on creating diagnostic tests to aid in classification, prognostication and therapeutics. In collaboration with his colleagues at UPMC, he has developed a diagnostic platform for the evaluation of fluid and cellular specimens from pancreatic cysts for the early detection of pancreatic cancer. Dr. Singhi’s project involves collaboration with Pancreatic Cancer Action Network research grant recipient and Scientific and Medical Advisory Board member Anirban Maitra, MBBS, and grantee Eugene Koay, MD, PhD.
It is reported that pancreatic cysts are identified in 1.2 to 2.6 percent of all abdominal computed tomography (CT) scans. Many of these cysts are benign and can be monitored clinically. In contrast, mucinous cysts can progress to pancreatic ductal adenocarcinoma, the most common and most aggressive form of pancreatic cancer. However, most mucinous cysts are slow-growing, with a minority undergoing malignant transformation into invasive tumors. There is a dire need for diagnostic markers that enable differentiation of various types of cysts and determination of a cyst’s likelihood to progress to pancreatic cancer.
The transformation of mucinous cysts into invasive pancreatic tumors occurs through a series of genetic changes. Some of these genetic changes can be detectable in samples of fluid extracted from cysts via endoscopic ultrasound. Dr. Singhi and his research team previously tested a panel of candidate genetic changes in more than 300 pancreatic cyst fluid samples. Using the presence or absence of these abnormalities as their criteria, the test correctly identified mucinous cysts 90 percent of the time, and the test was accurate every time it defined a cyst as non-mucinous. Further, their test was correct 83 percent of the time when detecting suspected precancerous abnormalities. Finally, the diagnosis of cysts can be enhanced even more through thorough, quantitative analysis of cross-sectional imaging from CT scans that assigns the cyst a numerical score.
Dr. Singhi and his colleagues therefore hypothesize that combining genetic markers and quantitative imaging will increase the diagnostic accuracy of identifying early cancer in a mucinous cyst. Specifically, they propose to expand the panel of pancreatic cancer-associated genetic abnormalities and utilize quantitative imaging analysis on fluid samples and cyst CT scans from patients with previously diagnosed and defined pancreatic cysts, in order to increase the accuracy of their test. Next, they will conduct a prospective (forward-looking) validation of their strategy in individuals being followed for pancreatic cysts of unknown type and undefined malignant potential. The goal is to generate a defined panel of genes and imaging markers that can be used as a diagnostic test. Ultimately, Dr. Singhi aims for rational stratification of patients to accurately identify, as quickly as possible, which patients will benefit from continued surveillance (watch and wait), and which patients need early surgical intervention for their pancreatic cysts.