Clonality and TP53 Mutation Analysis of Focal Nodular Hyperplasia of the Liver
KB Hodges, S Zheng, OW Cummings, R Saxena, S Zhang, M Wang, L Cheng. Indiana University School of Medicine, Indianapolis, IN; North China Coal Medical College, Tangshan, China
Background: Focal nodular hyperplasia (FNH) is considered a benign tumor of the liver. The pathogenesis and biologic nature of FNH is not clear. It has been proposed that FNH might be a benign reactive lesion related to hyperperfusion of blood caused by local arterial malformation. However, the clonality status of FNH is not well established. We sought to determine the clonality and TP53 mutation status of FNH to better characterize the nature of FNH in these patients.
Design: We analyzed 15 cases of FNH from female patients who underwent surgical resection of their lesions. All cases of FNH were diagnosed according to published criteria; all cases showed classic FNH features. Laser-capture microdissection of tumor and normal tissue from each patient was performed on sections with a PixCell II Laser Capture Microdissection system. Cell clusters were microdissected from multiple separate locations within a nodule of FNH to avoid the artifact of a monoclonal patch. Approximately 600-1000 cells of each FNH were microdissected from 5 micron histological sections. Normal tissue microdissected from the same patient was used as a control. The dissected tissue was incubated overnight in digestion buffer and proteinase K at 37°C. Genomic DNA was extracted and analyzed for X-chromosome inactivation status and TP53 mutations in exons 5, 7 and 8 by direct DNA sequencing. Correlations between clonality and different clinical variables were analyzed using chi-square test. A p-value of 0.05 was considered significant.
Results: The patients' age ranged from 16 to 54 (mean, 36 years). The sizes of the lesions ranged from 2 to 11.7 cm (mean, 5.1 cm). None had history of hepatitis viral infection or cirrhosis. Thirteen out of 15 cases (87%) were informative in our X-chromosome inactivation analyses. A nonrandom X-chromosome inactivation pattern was observed in 4 of the 13 (31%) informative cases. A random pattern of X-chromosome inactivation was observed in 9 of 13 (69%) informative cases. The clonality status was not associated with any of the clinical-pathological parameters including age and nodule size. No TP53 mutations were detected in any of the cases.
Conclusions: Our data indicate that a significant proportion of FNH have a monoclonal origin, suggesting that these lesions are neoplastic in nature rather than reactive. The lack of mutation in the TP53 gene supports the notion that FNH is a benign entity.
Category: Liver & Pancreas
Monday, March 22, 2010 1:00 PM
Poster Session II # 194, Monday Afternoon