Khalid Asif, McGrath Kevin M, Zahid Maliha, Wilson Matt, Brody Debra, Swalsky Patricia, Moser Arthur J, Lee Kenneth K, Slivka Adam, Whitcomb David C, Finkelstein Sydney
VA Pittsburgh Health Care System, and Division of Gastroenterology and Hepatology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Clin Gastroenterol Hepatol. 2005 Oct;3(10):967-73. doi: 10.1016/s1542-3565(05)00409-x.
BACKGROUND & AIMS: Current methods to detect malignancy in mucinous cystic neoplasms of the pancreas remain inadequate. The role of detailed molecular analysis in this context was investigated.
Endoscopic ultrasound-guided pancreatic cyst aspirates were prospectively collected during a period of 19 months and studied for cytology, carcinoembryonic antigen level, and molecular analysis. Molecular evaluation incorporated DNA quantification (amount and quality), k-ras point mutation, and broad panel tumor suppressor linked microsatellite marker allelic loss analysis by using fluorescent capillary electrophoresis. The sequence of mutation acquisition was also calculated on the basis of a clonal expansion model, and comparison was made to the final pathology.
Thirty-six cysts with confirmed histology were analyzed. There were 11 malignant, 15 premalignant, and 10 benign cysts. Malignant cysts could be differentiated from premalignant cysts on the basis of fluid carcinoembryonic antigen level (P=.034), DNA quality (P=.009), number of mutations (P=.002), and on the sequence of mutations acquired (P<.001). Early k-ras mutation followed by allelic loss was the most predictive of a malignant cyst (sensitivity, 91%; specificity, 93%).
Malignant cyst fluid contains adequate DNA to allow mutational analysis. A first hit k-ras mutation followed by allelic loss is most predictive of the presence of malignancy in a pancreatic cyst. This approach should serve as an ancillary tool to the conventional work-up of pancreatic cysts. Cumulative amount and timing of detectable mutational damage can assist in diagnosis and clinical management.
目前检测胰腺黏液性囊性肿瘤恶性病变的方法仍不完善。本文研究了详细分子分析在此类肿瘤中的作用。
前瞻性收集19个月内通过内镜超声引导获取的胰腺囊肿抽吸物，进行细胞学、癌胚抗原水平及分子分析。分子评估包括DNA定量（数量和质量）、k-ras点突变，以及通过荧光毛细管电泳对广泛的肿瘤抑制相关微卫星标记等位基因缺失进行分析。还根据克隆扩增模型计算突变获得的序列，并与最终病理结果进行比较。
对36个组织学确诊的囊肿进行分析。其中有11个恶性囊肿、15个癌前囊肿和10个良性囊肿。根据囊液癌胚抗原水平（P = 0.034）、DNA质量（P = 0.009）、突变数量（P = 0.002）及获得的突变序列（P < 0.001），可将恶性囊肿与癌前囊肿区分开来。早期k-ras突变后伴随等位基因缺失对恶性囊肿的预测性最强（敏感性为91%；特异性为93%）。
恶性囊肿液含有足够的DNA用于突变分析。首次出现k-ras突变后伴随等位基因缺失对胰腺囊肿恶性病变的存在最具预测性。该方法应作为胰腺囊肿传统检查的辅助工具。可检测到的突变损伤的累积量和时间可协助诊断和临床管理。
