Direct histological processing of EUS biopsies enables rapid molecular biomarker analysis for interventional pancreatic cancer trials

被引：42

作者：

Brais, Rebecca J. ^{[2
]}

Davies, Susan E. ^{[2
]}

O'Donovan, Maria ^{[2
]}

Simpson, Ben W. ^{[3
]}

Cook, Natalie ^{[1
,4
]}

Darbonne, Walter C. ^{[5
]}

Chilcott, Sian ^{[2
]}

Lolkema, Martijn P. ^{[1
,4
,6
]}

Neesse, Albrecht ^{[1
]}

Lockley, Michelle ^{[7
]}

Corrie, Pippa G. ^{[4
]}

Jodrell, Duncan I. ^{[1
,4
]}

Praseedom, Raaj K. ^{[8
]}

Huguet, Emmanuel L. ^{[8
]}

Jah, Asif ^{[8
]}

Jamieson, Neville V. ^{[8
]}

de Sauvage, Frederic J. ^{[5
]}

Tuveson, David A. ^{[1
,4
]}

Carroll, Nicholas R. ^{[3
]}

机构：

[1] CRUK, Cambridge Res Inst, Cambridge CB2 0RE, England

[2] Addenbrookes Hosp, Dept Histopathol, Cambridge CB2 0QQ, England

[3] Addenbrookes Hosp, Dept Radiol, Cambridge CB2 0QQ, England

[4] Addenbrookes Hosp, Dept Oncol, Cambridge CB2 0QQ, England

[5] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA

[6] Univ Med Ctr Utrecht, Dept Med Oncol Utrecht, NL-3508 GA Utrecht, Netherlands

[7] Queen Mary Univ London, Bans Canc Inst, John Vane Sci Ctr, London EC1M 6BQ, England

[8] Addenbrookes Hosp, Dept Surg, Hepatopancreatobiliary Unit, Cambridge CB2 0QQ, England

来源：

PANCREATOLOGY | 2012年 / 12卷 / 01期

关键词：

Pancreatic tumours; Endoscopic ultrasound (EUS); Fine needle aspiration (FNA) histology; Diagnostic biomarkers; Molecular pathology; FINE-NEEDLE-ASPIRATION; ENDOSCOPIC ULTRASOUND; GUIDED FNA; YIELD; CARCINOMA; MASSES; CYTOPATHOLOGIST; COMPLICATIONS; EXPERIENCE; DIAGNOSIS;

D O I：

10.1016/j.pan.2011.12.009

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Objective: Current practice to diagnose pancreatic cancer is accomplished by endoscopic ultrasound guided fine needle aspiration (EUS-FNA) using a cytological approach. This method is time consuming and often fails to provide suitable specimens for modern molecular analyses. Here, we compare the cytological approach with direct formalin fixation of pancreatic EUS-FNA micro-cores and evaluate the potential to perform molecular biomarker analysis on these specimen. Methods: 130 specimens obtained by EUS-FNA with a 22G needle were processed by the standard cytological approach and compared to a separate cohort of 130 specimens that were immediately formalin fixed to preserve micro-cores of tissue prior to routine histological processing. Results: We found that direct formalin fixation significantly shortened the time required for diagnosis from 3.6 days to 2.9 days (p < 0.05) by reducing the average time (140 vs 33 min/case) and number of slides (9.65 vs 4.67 slides/case) for histopathological processing. Specificity and sensitivity yielded comparable results between the two approaches (82.3% vs 77% and 90.9% vs 100%). Importantly, EUS-FNA histology preserved the tumour tissue architecture with neoplastic glands embedded in stroma in 67.89% of diagnostic cases compared to 27.55% with the standard cytological approach (p < 0.001). Furthermore, micro-core samples were suitable for molecular studies including the immunohistochemical detection of intranuclear Hes1 in malignant cells, and the laser-capture microdissection-mediated measurement of Gli-1 mRNA in tumour stromal myofibroblasts. Conclusions: Direct formalin fixation of pancreatic EUS-FNA micro-cores demonstrates superiority regarding diagnostic delay, costs, and specimen suitability for molecular studies. We advocate this approach for future investigational trials in pancreatic cancer patients. Copyright (C) 2012, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.

引用

页码：8 / 15

页数：8

共 28 条

[1] The clinical utility of endoscopic ultrasound-guided fine-needle aspiration in the diagnosis and staging of pancreatic carcinoma [J].

Chang, KJ ;

Nguyen, P ;

Erickson, RA ;

Durbin, TE ;

Katz, KD .

GASTROINTESTINAL ENDOSCOPY, 1997, 45 (05) :387-393

[2] Maximizing the yield of EUS-guided fine-needle aspiration [J].

Chang, KJ .

GASTROINTESTINAL ENDOSCOPY, 2002, 56 (04) :S28-S34

[3]

Cochrane H, 2005, GUIDELINES STAFFING

[4] Yield of endoscopic ultrasound-guided fine-needle aspiration biopsy in patients with suspected pancreatic carcinoma - Emphasis on atypical, suspicious, and false-negative aspirates [J].

Eloubeidi, MA ;

Jhala, D ;

Chhieng, DC ;

Chen, VK ;

Eltoum, I ;

Vickers, S ;

Wilcox, CM ;

Jhala, N .

CANCER CYTOPATHOLOGY, 2003, 99 (05) :285-292

[5] Endoscopic ultrasound-guided fine needle aspiration biopsy of patients with suspected pancreatic cancer: Diagnostic accuracy and acute and 30-day complications [J].

Eloubeidi, MA ;

Chen, VK ;

Eltoum, IA ;

Jhala, D ;

Chhieng, DC ;

Jhala, N ;

Vickers, SM ;

Wilcox, CM .

AMERICAN JOURNAL OF GASTROENTEROLOGY, 2003, 98 (12) :2663-2668

[6] Laser-capture microdissection [J].

Espina, Virginia ;

Wulfkuhle, Julia D. ;

Calvert, Valerie S. ;

VanMeter, Amy ;

Zhou, Weidong ;

Coukos, George ;

Geho, David H. ;

Petricoin, Emanuel F., III ;

Liotta, Lance A. .

NATURE PROTOCOLS, 2006, 1 (02) :586-603

[7] EUS-guided FNA: better samples with smaller needles? [J].

Gerke, Henning .

GASTROINTESTINAL ENDOSCOPY, 2009, 70 (06) :1098-1100

[8] Growth factor-dependent activation of the Ras-Raf-MEK-MAPK pathway in the human pancreatic carcinoma cell line PANC-1 carrying activated K-ras:: implications for cell proliferation and cell migration [J].

Giehl, K ;

Skripczynski, B ;

Mansard, A ;

Menke, A ;

Gierschik, P .

ONCOGENE, 2000, 19 (25) :2930-2942

[9] Endoscopic ultrasound elastography: the first step towards virtual biopsy? Preliminary results in 49 patients [J].

Giovannini, M ;

Hookey, LC ;

Bories, E ;

Pesenti, C ;

Monges, G ;

Delpero, JR .

ENDOSCOPY, 2006, 38 (04) :344-348

[10] A randomized comparison of EUS-guided FNA versus CT or US-guided FNA for the evaluation of pancreatic mass lesions [J].

Horwhat, JD ;

Paulson, EK ;

McGrath, K ;

Branch, MS ;

Baillie, J ;

Tyler, D ;

Pappas, T ;

Enns, R ;

Robuck, G ;

Stiffler, H ;

Jowell, P .

GASTROINTESTINAL ENDOSCOPY, 2006, 63 (07) :966-975

← 1 2 3 →