Agarwal Banke, Ludwig Olivia J, Collins Brian T, Cortese Cherise
Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, Missouri 63110, USA.
Clin Gastroenterol Hepatol. 2008 Dec;6(12):1425-31. doi: 10.1016/j.cgh.2008.08.010. Epub 2008 Aug 19.
BACKGROUND & AIMS: Serial analysis of gene expression has helped identify several proteins that are expressed differentially in pancreatic cancer and are highly sensitive and specific for pancreatic adenocarcinoma. We evaluated if the diagnostic accuracy of pancreatic cancer from endoscopic ultrasound (EUS)-fine-needle aspiration (FNA) can be improved by combined evaluation of cytology and immunostaining with these markers.
This study involved the use of archived specimens from patients treated at Saint Louis University Hospital from 2002 to 2006. We identified 5 protein markers that appeared most promising from published literature. We sequentially evaluated immunostaining with these markers in (1) surgical resection specimens, (2) cell blocks from EUS-FNA, and (3) direct smears of EUS-FN aspirates. Finally, we performed a combined evaluation of cytology and immunostaining in direct smears that were difficult to interpret and required a second consultative cytologic opinion.
In resection specimens, the majority of pancreatic adenocarcinomas expressed all 5 markers but fascin, maspin, and carcinoembryonic antigen-related cell adhesion molecule 6 also were expressed abnormally in normal pancreata and in chronic pancreatitis. Further evaluation therefore was limited to the other 2 markers: mesothelin and 14-3-3sigma. It was feasible and useful to perform immunostaining in cell blocks and direct smear for diagnosing pancreatic cancer. In cases requiring a second cytologic consultation, a combined evaluation of cytologic morphology and immunostaining had 90% accuracy for a pancreatic adenocarcinoma diagnosis.
In conclusion, immunostaining with newer protein markers is feasible in EUS-FNA specimens and can assist cytopathologists in diagnosing pancreatic cancer. Among the currently available protein immunomarkers, a combination of mesothelin and 14-3-3sigma seems most promising, but needs to be validated in prospective studies before routine clinical use.
基因表达系列分析有助于识别几种在胰腺癌中差异表达且对胰腺腺癌具有高度敏感性和特异性的蛋白质。我们评估了通过联合评估这些标志物的细胞学和免疫染色，是否能够提高内镜超声（EUS）细针穿刺活检（FNA）诊断胰腺癌的准确性。
本研究使用了2002年至2006年在圣路易斯大学医院接受治疗的患者的存档标本。我们从已发表的文献中确定了5种最具潜力的蛋白质标志物。我们依次评估了这些标志物在（1）手术切除标本、（2）EUS-FNA的细胞块和（3）EUS-FN吸取物的直接涂片上的免疫染色情况。最后，我们对难以解读且需要二次会诊细胞学意见的直接涂片进行了细胞学和免疫染色的联合评估。
在切除标本中，大多数胰腺腺癌表达所有5种标志物，但丝状肌动蛋白、乳腺丝抑蛋白和癌胚抗原相关细胞黏附分子6在正常胰腺和慢性胰腺炎中也有异常表达。因此，进一步的评估仅限于其他2种标志物：间皮素和14-3-3σ。在细胞块和直接涂片上进行免疫染色以诊断胰腺癌是可行且有用的。在需要二次细胞学会诊的病例中，细胞学形态和免疫染色的联合评估对胰腺腺癌诊断的准确率为90%。
总之，使用新型蛋白质标志物进行免疫染色在EUS-FNA标本中是可行的，并且可以帮助细胞病理学家诊断胰腺癌。在目前可用的蛋白质免疫标志物中，间皮素和14-3-3σ的组合似乎最有前景，但在常规临床应用前需要在前瞻性研究中进行验证。
