Winner Megan, Sethi Amrita, Poneros John M, Stavropoulos Stavros N, Francisco Peter, Lightdale Charles J, Allendorf John D, Stevens Peter D, Gonda Tamas A
Department of Surgery, Columbia University. New York, NY, USA.
JOP. 2015 Mar 20;16(2):143-9. doi: 10.6092/1590-8577/2941.
Molecular analysis of pancreatic cyst fluid obtained by EUS-FNA may increase diagnostic accuracy. We evaluated the utility of cyst-fluid molecular analysis, including mutational analysis of K-ras, loss of heterozygosity (LOH) at tumor suppressor loci, and DNA content in the diagnoses and surveillance of pancreatic cysts.
We retrospectively reviewed the Columbia University Pancreas Center database for all patients who underwent EUS/FNA for the evaluation of pancreatic cystic lesions followed by surgical resection or surveillance between 2006-2011. We compared accuracy of molecular analysis for mucinous etiology and malignant behavior to cyst-fluid CEA and cytology and surgical pathology in resected tumors. We recorded changes in molecular features over serial encounters in tumors under surveillance. Differences across groups were compared using Student's t or the Mann-Whitney U test for continuous variables and the Fisher's exact test for binary variables.
Among 40 resected cysts with intermediate-risk features, molecular characteristics increased the diagnostic yield of EUS-FNA (n=11) but identified mucinous cysts less accurately than cyst fluid CEA (P=0.21 vs. 0.03). The combination of a K-ras mutation and ≥2 loss of heterozygosity was highly specific (96%) but insensitive for malignant behavior (50%). Initial data on surveillance (n=16) suggests that molecular changes occur frequently, and do not correlate with changes in cyst size, morphology, or CEA.
In intermediate-risk pancreatic cysts, the presence of a K-ras mutation or loss of heterozygosity suggests mucinous etiology. K-ras mutation plus ≥2 loss of heterozygosity is strongly associated with malignancy, but sensitivity is low; while the presence of these mutations may be helpful, negative findings are uninformative. Molecular changes are observed in the course of cyst surveillance, which may be significant in long-term follow-up.
通过超声内镜引导下细针穿刺（EUS-FNA）获取胰腺囊肿液进行分子分析可能会提高诊断准确性。我们评估了囊肿液分子分析在胰腺囊肿诊断和监测中的效用，包括K-ras突变分析、肿瘤抑制基因座杂合性缺失（LOH）以及DNA含量分析。
我们回顾性分析了哥伦比亚大学胰腺中心数据库中2006年至2011年间接受EUS/FNA评估胰腺囊性病变并随后接受手术切除或监测的所有患者。我们比较了分子分析对黏液性病因和恶性行为的诊断准确性与囊肿液癌胚抗原（CEA）、细胞学检查以及切除肿瘤的手术病理结果。我们记录了接受监测的肿瘤在连续检查中分子特征的变化。使用Student's t检验或Mann-Whitney U检验比较连续变量组间差异，使用Fisher精确检验比较二元变量组间差异。
在40个具有中等风险特征的切除囊肿中，分子特征提高了EUS-FNA的诊断率（n = 11），但在识别黏液性囊肿方面不如囊肿液CEA准确（P = 0.21对0.03）。K-ras突变与≥2个杂合性缺失的组合具有高度特异性（96%），但对恶性行为的敏感性较低（50%）。监测（n = 16）的初步数据表明分子变化频繁发生，且与囊肿大小、形态或CEA的变化无关。
在中等风险的胰腺囊肿中，K-ras突变或杂合性缺失提示黏液性病因。K-ras突变加≥2个杂合性缺失与恶性肿瘤密切相关，但敏感性较低；虽然这些突变的存在可能有帮助，但阴性结果并无参考价值。在囊肿监测过程中可观察到分子变化，这在长期随访中可能具有重要意义。
