Khalid Asif, Nodit Laurentia, Zahid Maliha, Bauer Kathy, Brody Debra, Finkelstein Sydney D, McGrath Kevin M
Department of Medicine, The University of Pittsburgh and VA Pittsburgh Health Care, PA 15213, USA.
Am J Gastroenterol. 2006 Nov;101(11):2493-500. doi: 10.1111/j.1572-0241.2006.00740.x.
Accurate diagnosis of malignant and benign pancreatic masses can be challenging, potentially delaying treatment for cancer and subjecting patients with benign disease to unnecessary surgery. Endoscopic ultrasound fine needle aspirate (EUS-FNA) of pancreatic masses remains inconclusive in a subset of patients. The role of EUS-FNA molecular analysis in this context is studied.
Patients with benign pancreatic masses (6 cases, 4 autoimmune pancreatitis, 2 focal chronic pancreatitis) and malignant pancreatic masses (15) with inconclusive cytology (5 cases) and positive cytology (10 controls) were selected. All cases had definitive pathology. Representative cells were microdissected from each EUS-FNA sample and subjected to PCR for analysis of 16 microsatellite allele loss markers situated at 1p, 3p, 5q, 9p, 9q, 10q, 17p, 17q, 21q, and 22q. Loss of heterozygosity analysis used fluorescent capillary electrophoresis for quantitative determination of allelic imbalance. k-ras-2 point mutation analysis was also performed. Mean fractional mutation rate (FMR) was calculated and compared for each group.
All malignant cases carried multiple mutations (FMR 0.50), regardless of positive cytology (FMR 0.52) or suspicious cytology (FMR 0.47) (p = NS). Five of the 6 benign cases carried no mutations whereas 1 case of autoimmune pancreatitis and coexisting PanIN lesions exhibited a k-ras mutation (FMR 0.01). The mean FMR for the malignant and benign samples was significantly different (p < 0.0001).
Broad panel microsatellite loss and k-ras point mutation analysis can be reliably performed on EUS-FNA samples from pancreatic masses and improves the diagnostic accuracy. Furthermore, it accurately differentiates between malignant and benign pancreatic masses.
准确诊断胰腺良恶性肿块具有挑战性，这可能会延误癌症治疗，并使良性疾病患者接受不必要的手术。胰腺肿块的内镜超声细针穿刺抽吸术（EUS-FNA）在一部分患者中仍无法得出明确结论。本研究探讨了EUS-FNA分子分析在此情况下的作用。
选取胰腺良性肿块患者6例（4例自身免疫性胰腺炎，2例局灶性慢性胰腺炎）和胰腺恶性肿块患者15例，其中细胞学检查结果不明确的5例，细胞学检查结果阳性的10例作为对照。所有病例均有明确的病理诊断。从每个EUS-FNA样本中显微切割出代表性细胞，并进行聚合酶链反应（PCR），以分析位于1p、3p、5q、9p、9q、10q、17p、17q、21q和22q的16个微卫星等位基因缺失标记。杂合性缺失分析采用荧光毛细管电泳法定量测定等位基因失衡。还进行了k-ras-2点突变分析。计算并比较每组的平均分数突变率（FMR）。
所有恶性病例均有多个突变（FMR 0.50），无论细胞学检查结果阳性（FMR 0.52）还是可疑（FMR 0.47）（p =无显著性差异）。6例良性病例中有5例无突变，而1例自身免疫性胰腺炎合并胰腺上皮内瘤变（PanIN）病变出现k-ras突变（FMR 0.01）。恶性和良性样本的平均FMR有显著差异（p < 0.0001）。
对胰腺肿块的EUS-FNA样本进行广泛的微卫星缺失和k-ras点突变分析可以可靠地进行，并提高诊断准确性。此外，它能准确区分胰腺良恶性肿块。
