Bournet Barbara, Selves Janick, Grand David, Danjoux Marie, Hanoun Naima, Cordelier Pierre, Buscail Louis
*Department of Gastroenterology †INSERM UMR 1037, CHU Toulouse Rangueil ‡Department of Pathology, CHU Toulouse Purpan, University of Toulouse, Toulouse, France.
J Clin Gastroenterol. 2015 Jan;49(1):50-6. doi: 10.1097/MCG.0000000000000053.
Mutation of the KRAS oncogene is present in 75% to 95% of pancreatic cancer tissues. This study aimed to evaluate whether endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), combined with analysis of the KRAS mutation, improves the diagnosis of pancreatic cancer in cases of inconclusive or doubtful cytopathologic analysis.
We prospectively included 186 patients with a pancreatic mass (103 men; mean age: 62 y). Cytopathology and KRAS mutations, using TaqMan MGB allelic discrimination, were performed on EUS-FNA material. A final diagnosis was obtained from EUS-FNA analysis and/or a subsequent biopsy if necessary, and/or surgery, and follow-up: these were pancreatic adenocarcinoma (n=104), other malignant pancreatic tumors (n=22), and benign lesions (n=60, including 35 cases of chronic pancreatitis).
Inconclusive or doubtful (low-grade dysplasia or atypia) cytopathology was found in 68 cases. Of these, 29 patients who had adenocarcinoma were subsequently diagnosed, including 19 cases with a former KRAS mutation. Sensitivity, specificity, positive and negative predictive values, and overall accuracy of cytopathology alone to diagnose adenocarcinoma were 73%, 100%, 100%, 75%, and 85%, respectively. When KRAS mutation analysis was combined with pathology, these values reached 88%, 99%, 99%, 89%, and 93%, respectively. The performance of EUS-FNA to diagnose malignancy was similarly improved after the KRAS-mutation assay (negative predictive value increased from 67% to 88%; accuracy increased from 85% to 94%).
EUS-FNA plus KRAS-mutation analysis, using allelic discrimination, is accurate and improves the diagnosis of pancreatic adenocarcinoma when pathology is inconclusive or doubtful.
KRAS癌基因的突变存在于75%至95%的胰腺癌组织中。本研究旨在评估内镜超声引导下细针穿刺活检（EUS-FNA）联合KRAS突变分析，能否在细胞病理学分析结果不确定或可疑的情况下提高胰腺癌的诊断率。
我们前瞻性纳入了186例胰腺肿物患者（男性103例；平均年龄：62岁）。对EUS-FNA获取的样本进行细胞病理学检查及采用TaqMan MGB等位基因鉴别技术检测KRAS突变。最终诊断通过EUS-FNA分析和/或必要时的后续活检和/或手术获得，并进行随访：这些患者包括胰腺腺癌（n = 104）、其他胰腺恶性肿瘤（n = 22）和良性病变（n = 60，包括35例慢性胰腺炎）。
68例患者的细胞病理学检查结果不确定或可疑（低级别发育异常或异型性）。其中，29例后来被诊断为腺癌的患者，包括19例之前检测到KRAS突变的患者。单独依靠细胞病理学诊断腺癌的敏感性、特异性以及阳性和阴性预测值、总体准确率分别为73%、100%、100%、75%和85%。当KRAS突变分析与病理学检查相结合时，这些数值分别达到88%、99%、99%、89%和93%。在进行KRAS突变检测后，EUS-FNA诊断恶性肿瘤的效能同样得到提高（阴性预测值从67%提高到88%；准确率从85%提高到94%）。
当病理学检查结果不确定或可疑时，采用等位基因鉴别技术的EUS-FNA联合KRAS突变分析准确有效，可提高胰腺腺癌的诊断率。
