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Endoscopy 2006; 38: 50-53
DOI: 10.1055/s-2006-946652
Invited papers
Pancreato-biliary tumors
© Georg Thieme Verlag KG Stuttgart · New York

Molecules and markers for endosonographers: What do we need to know and measure?

M. Al-Haddad1 , M. B. Wallace1
  • 1Division of Gastroentorology and Hepatology, Mayo Clinic College of Medicine, Jacksonville, FL
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Publication History

Publication Date:
26 June 2006 (online)

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Introduction

Endoscopic ultrasound (EUS) has become an indispensable tool for the diagnosis and staging for gastrointestinal and thoracic malignancies. Thanks to the safety and reliability of fine needle aspiration (FNA), this has become the method of choice for tissue acquisition from lymph nodes and tumors in various locations within the thoracic and abdominal cavities.

In the recent years, EUS-FNA has offered a better understanding of the pathophysiology of cancer. Similar to the adenoma-carcinoma sequence, other cancers including pancreas, lung, and esophagus may follow a comparable multi-step process of carcinogenesis. A necessary component of these is the ability to go ”beyond cytology” to use fine needle aspirates to characterize the genomic and proteomic profiles of cancer and precancerous tissue.

References

  • 1 Ilyin S E, Belkowski S M, Plata-Salaman C R. Biomarker discovery and validation: technologies and integrative approaches.  Trends Biotechnol. 2004;  22 (8) 411-416
    CrossrefPubMedGoogle Scholar
  • 2 Pritzker K P, Azad A. Genomic biomarkers for cancer assessment: implementation challenges for laboratory practice.  Clin Biochem. 2004;  37 (7) 642-646
    PubMedGoogle Scholar
  • 3 Brugge W R. Approach to cystic pancreatic lesions.  Gastrointest Endosc Clin N Am. 2005;  15 (3) 485-496, viii
    CrossrefPubMedGoogle Scholar
  • 4 Khalid A. et al . Use of microsatellite marker loss of heterozygosity in accurate diagnosis of pancreaticobiliary malignancy from brush cytology samples.  Gut. 2004;  53 (12) 1860-1865
    CrossrefPubMedGoogle Scholar
  • 5 McCarthy D M. et al . Novel markers of pancreatic adenocarcinoma in fine-needle aspiration: mesothelin and prostate stem cell antigen labeling increases accuracy in cytologically borderline cases.  Appl Immunohistochem Mol Morphol. 2003;  11 (3) 238-243
    PubMedGoogle Scholar
  • 6 Frossard J L. et al . Performance of endosonography-guided fine needle aspiration and biopsy in the diagnosis of pancreatic cystic lesions.  Am J Gastroenterol. 2003;  98 (7) 1516-1524
    CrossrefPubMedGoogle Scholar
  • 7 Hammel P. et al . Diagnostic value of CA 72 - 4 and carcinoembryonic antigen determination in the fluid of pancreatic cystic lesions.  Eur J Gastroenterol Hepatol. 1998;  10 (4) 345-348
    CrossrefPubMedGoogle Scholar
  • 8 Brugge W R. et al . Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study.  Gastroenterology. 2004;  126 (4) 1330-1336
    CrossrefPubMedGoogle Scholar
  • 9 Goggins M. Molecular markers of early pancreatic cancer.  J Clin Oncol. 2005;  23 (20) 4524-4531
    CrossrefPubMedGoogle Scholar
  • 10 Matsubayashi H. et al . DNA methylation alterations in the pancreatic juice of patients with suspected pancreatic disease.  Cancer Res. 2006;  66 (2) 1208-1217
    CrossrefPubMedGoogle Scholar
  • 11 Wilentz R E. et al . K-ras mutations in the duodenal fluid of patients with pancreatic carcinoma.  Cancer. 1998;  82 (1) 96-103
    CrossrefPubMedGoogle Scholar
  • 12 Yamada T. et al . Detection of K-ras gene mutations in plasma DNA of patients with pancreatic adenocarcinoma: correlation with clinicopathological features.  Clin Cancer Res. 1998;  4 (6) 1527-1532
    PubMedGoogle Scholar
  • 13 Ohuchida K. et al . A highly sensitive and quantitative telomerase activity assay with pancreatic juice is useful for diagnosis of pancreatic carcinoma without problems due to polymerase chain reaction inhibitors: analysis of 100 samples of pancreatic juice from consecutive patients.  Cancer. 2004;  101 (10) 2309-2317
    CrossrefPubMedGoogle Scholar
  • 14 Myung S J. et al . Telomerase activity in pure pancreatic juice for the diagnosis of pancreatic cancer may be complementary to K-ras mutation.  Gastrointest Endosc. 2000;  51 (6) 708-713
    CrossrefPubMedGoogle Scholar
  • 15 Brunner T B. et al . Pancreatic cancer cell radiation survival and prenyltransferase inhibition: the role of K-Ras.  Cancer Res. 2005;  65 (18) 8433-8441
    CrossrefPubMedGoogle Scholar
  • 16 Caldas C. et al . Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma.  Nat Genet. 1994;  8 (1) 27-32
    CrossrefPubMedGoogle Scholar
  • 17 Kalthoff H. et al . p53 and K-RAS alterations in pancreatic epithelial cell lesions.  Oncogene. 1993;  8 (2) 289-298
    PubMedGoogle Scholar
  • 18 Tada M. et al . Detection of ras gene mutations in pancreatic juice and peripheral blood of patients with pancreatic adenocarcinoma.  Cancer Res. 1993;  53 (11) 2472-2474
    PubMedGoogle Scholar
  • 19 Mulcahy H E. et al . A prospective study of K-ras mutations in the plasma of pancreatic cancer patients.  Clin Cancer Res. 1998;  4 (2) 271-275
    PubMedGoogle Scholar
  • 20 Shi C. et al . LigAmp for sensitive detection of single-nucleotide differences.  Nat Methods. 2004;  1 (2) 141-147
    CrossrefPubMedGoogle Scholar
  • 21 Caldas C. et al . Detection of K-ras mutations in the stool of patients with pancreatic adenocarcinoma and pancreatic ductal hyperplasia.  Cancer Res. 1994;  54 (13) 3568-3573
    PubMedGoogle Scholar
  • 22 Hollstein M. et al . p53 mutations in human cancers.  Science. 1991;  253 (5015) 49-53
    CrossrefPubMedGoogle Scholar
  • 23 Sturm P D. et al . The potential diagnostic use of K-ras codon 12 and p53 alterations in brush cytology from the pancreatic head region.  J Pathol. 1998;  186 (3) 247-253
    PubMedGoogle Scholar
  • 24 Itoi T. et al . Immunohistochemical analysis of p53 and MIB-1 in tissue specimens obtained from endoscopic ultrasonography-guided fine needle aspiration biopsy for the diagnosis of solid pancreatic masses.  Oncol Rep. 2005;  13 (2) 229-234
    PubMedGoogle Scholar
  • 25 Franquemont D W. Differentiation and risk assessment of gastrointestinal stromal tumors.  Am J Clin Pathol. 1995;  103 (1) 41-47
    CrossrefPubMedGoogle Scholar
  • 26 Rosch T. et al . Endosonographic diagnosis of submucosal upper gastrointestinal tract tumors.  Scand J Gastroenterol. 1992;  27 (1) 1-8
    PubMedGoogle Scholar
  • 27 Miettinen M, Virolainen M, Maarit Sarlomo R. Gastrointestinal stromal tumors-value of CD34 antigen in their identification and separation from true leiomyomas and schwannomas.  Am J Surg Pathol. 1995;  19 (2) 207-216
    PubMedGoogle Scholar
  • 28 Kindblom L G. et al . Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal.  Am J Pathol. 1998;  152 (5) 1259-1269
    PubMedGoogle Scholar
  • 29 Boyce G A. et al . Evaluation of submucosal upper gastrointestinal tract lesions by endoscopic ultrasound.  Gastrointest Endosc. 1991;  37 (4) 449-454
    CrossrefPubMedGoogle Scholar
  • 30 DeMatteo R P. et al . Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival.  Ann Surg. 2000;  231 (1) 51-58
    CrossrefPubMedGoogle Scholar
  • 31 Wiersema M J. et al . Endosonography-guided fine-needle aspiration biopsy: diagnostic accuracy and complication assessment.  Gastroenterology. 1997;  112 (4) 1087-1095
    PubMedGoogle Scholar
  • 32 Matsui M. et al . Preliminary results of fine needle aspiration biopsy histology in upper gastrointestinal submucosal tumors.  Endoscopy. 1998;  30 (9) 750-755
    Article in Thieme ConnectPubMedGoogle Scholar
  • 33 Amin M B. et al . Prognostic value of proliferating cell nuclear antigen index in gastric stromal tumors. Correlation with mitotic count and clinical outcome.  Am J Clin Pathol. 1993;  100 (4) 428-432
    PubMedGoogle Scholar
  • 34 Carrillo R. et al . Prognostic significance of DNA ploidy and proliferative index (MIB-1 index) in gastrointestinal stromal tumors.  Hum Pathol. 1997;  28 (2) 160-165
    CrossrefPubMedGoogle Scholar
  • 35 Sarlomo-Rikala M. et al . CD117: a sensitive marker for gastrointestinal stromal tumors that is more specific than CD34.  Mod Pathol. 1998;  11 (8) 728-734
    PubMedGoogle Scholar
  • 36 Graadt van Roggen J F, van Velthuysen M L, Hogendoorn P C. The histopathological differential diagnosis of gastrointestinal stromal tumours.  J Clin Pathol. 2001;  54 (2) 96-102
    CrossrefPubMedGoogle Scholar
  • 37 Ueyama T. et al . A clinicopathologic and immunohistochemical study of gastrointestinal stromal tumors.  Cancer. 1992;  69 (4) 947-955
    CrossrefPubMedGoogle Scholar
  • 38 Seidal T, Edvardsson H. Expression of c-kit (CD117) and Ki67 provides information about the possible cell of origin and clinical course of gastrointestinal stromal tumours.  Histopathology. 1999;  34 (5) 416-424
    CrossrefPubMedGoogle Scholar
  • 39 Newman P L, Wadden C, Fletcher C D. Gastrointestinal stromal tumours: correlation of immunophenotype with clinicopathological features.  J Pathol. 1991;  164 107 (2)-117
    PubMedGoogle Scholar
  • 40 Ando N. et al . The diagnosis of GI stromal tumors with EUS-guided fine needle aspiration with immunohistochemical analysis.  Gastrointest Endosc. 2002 ;  55 (1) 37-43
    CrossrefPubMedGoogle Scholar

Michael B. Wallace, M.D.

Associate Professor of Medicine

Division of Gastroenterology and Hepatology

Mayo Clinic Jacksonville

4500 San Pablo Rd

Jacksonville, FL 32224

Email: wallace.michael@mayo.edu