Detection of KRAS Mutation and Loss of Heterozygosity (LOH) in Mucinous Nonneoplastic Cyst of the Pancreas.
Bing Zhu, Sydney D Finkelstein, Zhongming Chen, Xiaoqi Lin. Northwestern University, Chicago; RedPath Integrated Pathology, Inc, Pittsburgh
Background: Mucinous nonneoplastic cyst (MNNC) of the pancreas is defined as cysts lined by mucinous epithelium and supported by hypocellular stroma with no communication with the pancreatic ducts. MNNC is a rare and not well recognized entity with unknown histogenesis and etiology. It shares many clinical and radiological features with mucinous cystic neoplasm (MCN) and intraductal papillary mucinous neoplasm (IPMN), particularly the branch type, therefore, creating great diagnostic challenge for cytological evaluation of FNA specimens. To explore a petential role of molecular test in aiding diagnosis and distinguish it from MCN and IPMN, we analyzed KRAS mutation and LOH in MNNC.
Design: 24 surgically resected MNNCs were retrieved. The cystic lining epithelium was microdissected for molecular tests: 1) KRAS mutation (1st exon) (DNA sequencing), and 2) allelic imbalance (LOH) for a panel of 16 polymorphic microsatellite repeat markers targeting tumor suppressor genes and situated at 1p, 3p, 5q, 9p, 10q, 17p, 17q, 18q, 21q, and 22q. Cystic fluid CEA and amylase concentrations were also retrieved.
Results: CEA ranged from 75.2 to 5,488 ng/ml and amylase from 19 to 28,478 U/L. Molecular studies on 15 of 24 cases showed that 4 cases had 1 genomic mutation, 1 with KRAS mutation at 12D (40% of cells), 1 with KRAS mutation at 12R (20% of cells), 1 with LOH at 10q (50% of cells), and 1 with LOH at 17q (60% of cells).
Conclusions: Detection of CEA and amylase levels in cystic fluid is not useful to distinguish MNNC from IPMN and MCN. Molecular study results indicated that 4 of 15 (27%) surgically diagnosed MNNCs acquired 1 low amplitude (< 75% of cells) genomic mutation, 2 K-RAS mutations, 1 LOH at 10q (pTEN) and 1 LOH at 17q (HER2/neu and NF1). Although the genomic mutation rate detected in MNNC is very low, the data indicated that rare MNNC may acquite genetic alteration similar to low grade pancreatic intraepithelial neoplasia (PaIN), fuming the debate of the true nature of these lesions.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 220, Wednesday Morning