407 Comparison of K-RAS-2 and LOH Mutational Analysis with Pancreas Cyst Fluid CEA Levels and Histology

Abstract

BACKGROUND: The main objective of pancreatic cyst fluid analysis is to differentiate cysts of mucinous or malignant variety from other cysts which have a benign course. Previous investigators have reported that K-ras-2 point mutation and at least two mutations of allelic imbalance or loss of heterozygosity (LOH) with good quality DNA is characteristic of mucinous cystic neoplasm (MCN). OBJECTIVE: Identify the clinical impact of DNA analysis of pancreatic cyst fluid with its correlation to cyst fluid chemistry and histologic analysis. METHODS: This is a retrospective analysis of all consecutive patients with pancreatic cysts who presented for endoscopic ultrasound (EUS) examination with fine-needle aspiration (FNA) biopsy over an 18 month period until October 2007. DNA analysis was performed by RedPath Integrated Pathology (Pittsburg, PA). Fluid analysis included carcinogenic embryonic antigen (CEA) with values >192ng/dL suggestive of MCN. The standard for comparison was surgical histopathology when available. RESULTS: 27 consecutive patients with cysts and samples submitted for DNA analysis were examined including 15 men and 12 women (mean age 62.8 and 61.3 years, respectively). In 20 patients, all parameters including cyst fluid, DNA analysis, and histology were available for comparison. Consistent findings were seen in 7/20 (35%) in which all parameters suggested negative benign findings. 3/20 (15%) had positive K-ras-2 mutations of which only 2/3 had true histologic MCN suggesting a 33% false positivity. 7/20 (35%) of patients had at least 2 LOH mutations; however only 2/7 were actually positive on histology for MCN suggesting 71% false positivity. In the same group, CEA levels >192ng/dL were seen in 7/20 of which 4/7 had histologic malignancy demonstrating 42.9% false positivity. In a group of 9 malignant cysts (MCN, side branch intraductal papillary mucinous neoplasm, and cystic degeneration of adenocarcinoma), 7 (78%) had CEA levels >192ng/dL. In this group, 7 had DNA analysis of which 4/7 (57.1%) were falsely negative for K-ras-2 and 3/7 (42.9%) falsely negative for LOH. CONCLUSIONS: Consistency in histology, CEA levels, and K-ras-2 and LOH mutations was seen in only 35% of cases, all of which were benign cysts. In the detection of malignant cysts, elevated CEA levels were more predictive of histology in comparison to K-ras-2 or LOH mutations. Additionally, false positivity of LOH mutations was noted to be considerably higher than K-ras-2mutations or even fluid CEA levels. These findings suggest that DNAmutation analysis should not be used routinely but rather selectively in the evaluation of pancreatic cysts.