Maluf-Filho Fauze, Kumar Atul, Gerhardt René, Kubrusly Márcia, Sakai Paulo, Hondo Fabio, Matuguma Sergio Eiji, Artifon Everson, Monteiro da Cunha José Eduardo, César Machado Marcel Cerqueira, Ishioka Shinichi, Forero Elias
Gastrointestinal Endoscopy Division, University of São Paulo School of Medicine, São Paulo, Brazil.
J Clin Gastroenterol. 2007 Nov-Dec;41(10):906-10. doi: 10.1097/MCG.0b013e31805905e9.
The accuracy of endoscopic ultrasound-fine needle aspiration cytology (EUS-FNAC) for the diagnosis of pancreatic cancer is suboptimal. Mutational activation of the kras oncogene is almost universally present in pancreatic cancer tissue. We, therefore, investigated if analysis for mutant kras gene in the EUS-FNAC aspirates supplements cytopathology for the diagnosis of pancreatic adenocarcinoma (PAC).
EUS-FNAC specimens obtained from 74 patients with pancreatic masses were analyzed for the presence of kras mutation on codon 12 using polymerase chain reaction-restriction fragment length polymorphism and MvaI restriction enzyme. Definitive diagnosis was based on surgical pathology or long-term follow-up (median 27.8 mo); 57 patients had PAC, 11 patient's chronic pancreatitis, and 9 patient's nonfunctioning neuroendocrine tumors.
Analysis of mutant kras gene in addition to cytopathology allowed the detection of PAC in 4 additional patients as compared with cytopathology alone. Cytopathology and kras mutant analysis were negative for PAC in 17 patients of whom 6 patients (35%) had PAC. The respective sensitivity (90.9% vs. 82.5%), specificity (47.6% vs. 97.9%), positive predictive value (89.5% vs. 83.8%), negative predictive value (98.1% vs. 94.1%), accuracy (89.2% vs. 58.8%) of cytopathology plus kras mutation versus cytopathology were numerically superior but did not reach statistical significance.
Analysis for the presence of mutant kras gene supplements conventional cytopathology for the diagnosis of PAC even without a cytopathologist in attendance and using only 3 needle passes. Among patients with negative cytopathology, the presence of kras mutation represents pancreatic cancer while the absence of kras mutation increases the possibility of benign lesion.
超声内镜引导下细针穿刺细胞学检查（EUS-FNAC）诊断胰腺癌的准确性欠佳。胰腺癌组织中几乎普遍存在kras癌基因的突变激活。因此，我们研究了EUS-FNAC抽吸物中突变kras基因的分析是否能辅助细胞病理学诊断胰腺腺癌（PAC）。
对74例胰腺肿块患者的EUS-FNAC标本进行分析，采用聚合酶链反应-限制性片段长度多态性和MvaI限制性内切酶检测第12密码子kras突变的存在情况。最终诊断基于手术病理或长期随访（中位随访时间27.8个月）；57例患者为PAC，11例为慢性胰腺炎，9例为无功能神经内分泌肿瘤。
与单纯细胞病理学检查相比，除细胞病理学检查外，对突变kras基因的分析还使另外4例患者检测出PAC。17例患者的细胞病理学检查和kras突变分析对PAC均为阴性，其中6例（35%）患有PAC。细胞病理学检查加kras突变分析与细胞病理学检查相比，各自的敏感性（90.9%对82.5%）、特异性（47.6%对97.9%）、阳性预测值（89.5%对83.8%）、阴性预测值（98.1%对94.1%）、准确性（89.2%对58.8%）在数值上更高，但未达到统计学显著性。
即使在没有细胞病理学家在场且仅穿刺3针的情况下，对突变kras基因存在情况的分析也能辅助传统细胞病理学诊断PAC。在细胞病理学检查为阴性的患者中，kras突变的存在提示胰腺癌，而kras突变的缺失增加了良性病变的可能性。
