Skip to main content

Advertisement

SpringerLink
Log in

Accuracy of differential diagnosis for pancreatic cancer is improved in the combination of RCAS1 and CEA measurements and cytology in pancreatic juice

  • Original Paper
  • Published:
Medical Molecular Morphology Aims and scope Submit manuscript

Abstract

Improvement of diagnostic accuracy for pancreatic cancer in pancreatic disease patients was investigated by examining the combination of three diagnostic methods, i.e., measurements of RCAS1 and CEA levels in pancreatic juice and pancreatic juice cytology. Pancreatic juice was collected from 12 pancreatic cancer (PC) and 26 non-PC patients. RCAS1 and CEA levels were measured by using ELISA. RCAS1 expression on surgically resected tissue was immunohistochemically examined for 2 PC patients. By setting the cutoff level of RCAS1 at 10 U/ml and that of CEA at 18.5 μg/ml, sensitivity of RCAS1 was 42% and that of CEA was 50%. On the other hand, sensitivity and specificity increased from 42% and 85% of RCAS1 alone to 75% and 85% in the examination of RCAS1 + CEA + cytology, and the false-negative rate was also reduced to 25% in this combination. Immunohistochemically, a patient with a high RCAS1 level in pancreatic juice had numerous RCAS1-positive tumor cells in the pancreatic juice. We concluded that RCAS1 and CEA measurements together with cytology in pancreatic juice would be a useful combination method for making a differential diagnosis of PC from non-PC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Wong JC, Lu DSK (2008) Staging of pancreatic adenocarcinoma by imaging studies. Clin Gastroenterol Hepatol 6:1301–1308

    Article  PubMed  Google Scholar 

  2. Strobel K, Heinrich S, Bhure U, Soyka J, Veit-Haibach P, Pestalozzi BC, Clavein PA, Hany TF (2008) Contrast-enhanced 18F-FDG PET/CT: 1-stop-shop imaging for assessing the respectability of pancreatic cancer. J Nucl Med 49:1408–1413

    Article  PubMed  Google Scholar 

  3. Canto MI, Goggins M, Hruban RH, Petersen GM, Giardiello FM, Yeo C, Fishman EK, Brune K, Axilbund J, Griffin C, Ali S, Richman J, Jagannath S, Kantsevoy SV, Kallon AN (2006) Screening for early pancreatic neoplasm in high-risk individuals: a prospective controlled study. Clin Gastroenterol Hepatol 4:766–781

    Article  PubMed  Google Scholar 

  4. Vandervoort J, Soetikno RM, Montes H, Lichtenstein DR, Van Dam J, Ruymann FW, Cibas ES, Carr-Locke DL (1999) Accuracy and complication rate of brush cytology from bile duct versus pancreatic duct. Gastrointest Endosc 49:322–327

    Article  PubMed  CAS  Google Scholar 

  5. Uchida N, Kamada H, Tsutsui K Ono M, Aritomo Y, Masaki T, Kushida Y, Haba R, Nakatsu T, Kuriyama S (2007) Utility of pancreatic duct brushing for diagnosis of pancreatic carcinoma. J Gastroenterol 42:657–662

    Article  PubMed  Google Scholar 

  6. Imamura T, Takeshita R, Koyama R, Okuda C, Takeuchi K, Matsuda M, Hashimoto M, Watanabe G, Yoshida H, Imawari M (2006) Effectiveness of cytodiagnosis with pancreatic duct lavage fluid for pancreatic ductal carcinoma: new sampling technique. Dig Endosc 18:303–307

    Article  Google Scholar 

  7. Yan L, McFaul C, Howes N, Leslie J, Lancaster G, Wong T, Threadgold J, Evans J, Glimore I, Smart H, Lombard M, Neoptolemos J, Greenhalf W (2005) Molecular analysis to detect pancreatic ductal adenocarcinoma in high-risk group. Gastroenterology 128: 2124–2130

    Article  PubMed  CAS  Google Scholar 

  8. Bian Y, Matsubayashi H, Li CP, Abe T, Canto M, Murphy KM, Goggins M (2006) Detecting low-abundance p16 and p53 mutation in pancreatic juice using a novel assay: heteroduplex analysis of limiting dilution PCRs. Cancer Biol Ther 5:1392–1399

    Article  PubMed  CAS  Google Scholar 

  9. Myung SJ, Kim MH, Kim YS Kim HJ, Park ET, Yoo KS, Lim BC, Wan Seo D, Lee SK, Min YI, Kim JY (2000) Telomerase activity in pure pancreatic juice for the diagnosis of pancreatic cancer may be complementary to K-ras mutation. Gastrointest Endosc 51: 708–713

    Article  PubMed  CAS  Google Scholar 

  10. Uehara H, Nakaizumi A, Iishi H, Takenaka A, Eguchi H, Ohigashi H, Ishikawa O (2008) In situ telomerase activity in pancreatic juice may discriminate pancreatic cancer from other pancreatic diseases. Pancreas 36:236–240

    Article  PubMed  CAS  Google Scholar 

  11. Hiraoka K, Hida Y, Miyamoto M, Oshikiri T, Suzuoki M, Nakakubo Y, Shinohara T, Itoh T, Shichinohe T, Kondo S, Kasahara N, Katoh H (2002) High expression of tumor-associated antigen RCAS1 in pancreatic ductal adenocarcinoma is an unfavorable prognostic marker. Int J Cancer 99:418–423

    Article  PubMed  CAS  Google Scholar 

  12. Kaku T, Sonoda K, Kamura T, Hirakawa T, Sakai K, Amada S, Ogawa S, Kobayashi H, Nakashima M, Watanabe T, Nakano H (1999) The prognostic significance of tumor-associated antigen 22-1-1 expression in adenocarcinoma of the uterine cervix. Clin Cancer Res 5:1449–1453

    PubMed  CAS  Google Scholar 

  13. Sonoda K, Kaku T, Hirakawa T, Kobayashi H, Amada S, Sakai K, Nakashima M, Watanabe T, Nakano H (2000) The clinical significance of tumor-associated antigen RCAS1 expression in the normal, hyperplastic, and malignant uterine endometrium. Gynecol Oncol 79:424–429

    Article  PubMed  CAS  Google Scholar 

  14. Takahashi H, Iizuka H, Nakashima M, Wada T, Asano K, Ishida-Yamamoto A, Watanabe T (2001) RCAS1 antigen is highly expressed in extramammary Paget’s disease and in advanced stage squamous cell carcinoma of the skin. J Dermatol Sci 26:140–144

    Article  PubMed  CAS  Google Scholar 

  15. Suzuki T, Inoue S, Kawabata W, Akahira J, Moriya T, Tsuchiya F, Ogawa S, Marumatsu M, Sasano H (2001) EBAG9/RCAS1 in human breast carcinoma: a possible factor in endocrine-immune interactions. Br J Cancer 85:1731–1737

    Article  PubMed  CAS  Google Scholar 

  16. Tsuneizumi M, Nagai H, Harada H, Kazui T, Emi M (2002) A highly polymorphic CA repeat marker at the EBAG9/RCAS1 locus on 8q23 that detected frequent multiplication in breast cancer. Ann Hum Biol 29:457–460

    Article  PubMed  Google Scholar 

  17. Noguchi K, Enjoji M, Nakamuta M, Nakashima M, Nishi H, Choi I, Taguchi K, Kotoh K, Shimada M, Sugimachi K, Tsuneyoshi M, Nawata H, Watanabe T (2001) Expression of a tumor-associated antigen RCAS1 in hepatocellular carcinoma. Cancer Lett 168: 197–202

    Article  PubMed  CAS  Google Scholar 

  18. Oshikiri T, Hida Y, Miyamoto M, Hashida H, Katoh K, Suzuoki M, Nakakubo Y, Hiraoka K, Shinohara T, Itoh T, Kondo S, Katoh H (2001) RCAS1 as a tumour progression marker: an independent negative prognostic factor in gallbladder cancer. Br J Cancer 85:1922–1927

    Article  PubMed  CAS  Google Scholar 

  19. Kubokawa M, Nakashima M, Yao T, Ito KI, Harada N, Nawata H, Watanabe T (2001) Aberrant intracellular localization of RCAS1 is associated with tumor progression of gastric cancer. Int J Oncol 19:695–700

    PubMed  CAS  Google Scholar 

  20. Ohshima K, Muta K, Nakashima M, Haraoka S, Tutiya T, Suzumiya J, Kawasaki C, Watanabe T, Kikuchi M (2001) Expression of human tumor-associated antigen RCAS1 in Reed-Sternberg cells in association with Epstein-Barr virus infection: a potential mechanism of immune evasion. Int J Cancer 93:91–96

    Article  PubMed  CAS  Google Scholar 

  21. Izumi M, Nakanishi Y, Yoshino I, Nakashima M, Watanabe T, Hara N (2001) Expression of tumor-associated antigen RCAS1 correlates significantly with poor prognosis in nonsmall cell lung carcinoma. Cancer (Phila) 92:446–451

    Article  CAS  Google Scholar 

  22. Nakashima M, Sonoda K, Watanabe T (1999) Inhibition of cell growth and induction of apoptotic cell death by the human tumorassociated antigen RCAS1. Nat Med 5:938–942

    Article  PubMed  CAS  Google Scholar 

  23. Enjoji M, Nakamuta M, Noguchi K, Sugimoto R, Kotoh K, Nawata H, Nakashima M, Watanabe T (2002) RCAS1 expression in immune-mediated liver diseases. J Clin Gastroenterol 34:286–287

    Article  PubMed  Google Scholar 

  24. Yamaguchi K, Enjoji M, Nakashima M, Nakamuta M, Watanabe T, Tanaka M (2005) Novel serum tumor marker, RCAS1, in pancreatic diseases. World J Gastroenterol 11:5199–5202

    PubMed  CAS  Google Scholar 

  25. Tanaka M, Chari S, Adsay V, Fernandez-del Castillo C, Falconi M, Shimizu M, Yamaguchi K, Yamao K, Matsuno S; International Association of Pancreatology (2006) International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology 6:17–32

    Article  PubMed  Google Scholar 

  26. Matsushima T, Nakashima M, Ohshima K, Abe Y, Nishimura J, Nawata H, Watanabe T, Muta K (2001) Receptor binding cancer antigen expressed on SiSo cells, a novel regulator of apoptosis of erythroid progenitor cells. Blood 98:313–321

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka, 830-0011, Japan

    Yoshiki Naito, Makiko Yasumoto, Jun Akiba, Koichi Ohshima & Hirohisa Yano

  2. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan

    Yoshinobu Okabe, Yusuke Ishida & Ryohei Kaji

  3. Department of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Science, Fukuoka University, Fukuoka, Japan

    Masakatsu Nagayama, Takuya Nishinakagawa, Kazuyuki Machida & Manabu Nakashima

  4. Department of Pathology, Kurume University Hospital, Kurume, Japan

    Tomoki Taira, Akihiko Kawahara & Masayoshi Kage

  5. Biostatistics Center, Kurume University, Kurume, Japan

    Satoshi Hattori

  6. Department of Surgery, Kurume University School of Medicine, Kurume, Japan

    Kazuhiro Mikagi & Hisafumi Kinoshita

Authors
  1. Yoshiki Naito
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshinobu Okabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masakatsu Nagayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takuya Nishinakagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tomoki Taira
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Akihiko Kawahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Satoshi Hattori
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kazuyuki Machida
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yusuke Ishida
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ryohei Kaji
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kazuhiro Mikagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Hisafumi Kinoshita
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Makiko Yasumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Jun Akiba
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Masayoshi Kage
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Manabu Nakashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Koichi Ohshima
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Hirohisa Yano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoshiki Naito.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Naito, Y., Okabe, Y., Nagayama, M. et al. Accuracy of differential diagnosis for pancreatic cancer is improved in the combination of RCAS1 and CEA measurements and cytology in pancreatic juice. Med Mol Morphol 44, 86–92 (2011). https://doi.org/10.1007/s00795-010-0511-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00795-010-0511-6

Key words

Search

Navigation