Skip to main content
SpringerLink
Log in

Clinical Significance of Tumor-associated Antigen RCAS1 Expression in Human Pancreatic Ductal Adenocarcinoma

  • Original Research
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a human tumor-associated antigen that induces cell cycle arrest and/or apoptosis in RCAS1 receptor-expressing immune cells. The aim of the present study was to evaluate the clinical significance of RCAS1 expression in human pancreatic adenocarcinoma. Immunohistochemical analysis of RCAS1 expression was performed on paraffin-embedded tissue sections obtained from 76 pancreatic adenocarcinoma patients. RCAS1 positivity and overexpression and intensity of the staining were correlated with clinicopathological parameters, proliferative capacity and patient survival. Of the 76 adenocarcinoma patients, 65 (86%) tested positive for RCAS1; of these 65 RCAS1-positive cases, 36 (55%) showed RCAS1 overexpression. RCAS1 positivity was statistically significantly correlated with the histopathological grade of the tumor (P = 0.026), and it showed a trend to be correlated with tumor size (P = 0.071). RCAS1 intensity and overexpression of staining showed a trend to be correlated with the histopathological grade of the tumor (P = 0.061 and P = 0.089, respectively), whereas RCAS1 positivity and the overexpression and intensity of staining were not statistically significantly correlated with the proliferative capacity of the tumor or any other clinicopathological parameter examined nor with patients’ survival. Our data provide evidence for the implication of RCAS1 in pancreatic neoplasia. However, the prediction of survival using RCAS1 expression as a marker seems uncertain for this type of cancer.

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

Fig. 1

Similar content being viewed by others

References

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

    Article  PubMed  CAS  Google Scholar 

  2. Sonoda K, Nakashima M, Kaku M, Kamura T, Nakano H, Watanabe T (1996) A novel tumor-associated antigen expressed in human uterine and ovarian carcinomas. Cancer 77:1501–1509

    Article  PubMed  CAS  Google Scholar 

  3. 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 

  4. Matsushima T, Nakashima M, Oshima 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 

  5. Akashi T, Oimomi H, Nishiyama K, Nakashima M, Arita Y, Sumii T, Kimura T, Ito T, Nawata H, Watanabe T (2003) Expression and diagnostic evaluation of the human tumor-associated antigen RCAS1 in pancreatic cancer. Pancreas 26:49–55

    Article  PubMed  CAS  Google Scholar 

  6. 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 

  7. 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 

  8. 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 

  9. 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 tumor progression marker: an independent negative prognostic factor in gallbladder cancer. Br J Cancer 85:1922–1927

    Article  PubMed  CAS  Google Scholar 

  10. 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 

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

    Article  Google Scholar 

  12. Okada K, Nakashima M, Komuta K, Hashimoto S, Okudaira S, Baba N, Hishikawa Y, Koji T, Kanematsu T, Watanabe T (2003) Expression of tumor-associated membrane antigen, RCAS1, in human colorectal carcinomas and possible role in apoptosis of tumor-infiltrating lymphocytes. Mol Pathol 16:679–685

    Article  Google Scholar 

  13. Tsujitani S, Saito H, Honboh T, Ataka M, Tanida T, Makino M, Ikeguchi M (2007) Prognostic significance of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) expression in relation to cadherin expression in patients with colorectal carcinoma. Dis Colon Rectum 50:1241–1249

    Article  PubMed  Google Scholar 

  14. Popiela TJ, Rudnicka-Sosin L, Dutsch-Wicherek M, Klimek M, Basta P, Galazka K, Wicherek L (2006) The metallothionein and RCAS1 expression analysis in breast cancer tissue regarding the immune cells presence and their activity. Neuro Endocrinol Lett 27:786–794

    PubMed  CAS  Google Scholar 

  15. Tsujitani S, Saito H, Oka S, Sakamoto T, Kanaji S, Tatebe S, Ikeguchi M (2007) Prognostic significance of RCAS1 expression in relation to the infiltration of dendritic cells and lymphocytes in patients with esophageal carcinoma. Dig Dis Sci 52:549–554

    Article  PubMed  CAS  Google Scholar 

  16. 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 in an unfavorable prognostic marker. Int J Cancer 99:418–423

    Article  PubMed  CAS  Google Scholar 

  17. Sonoda K, Miyamoto S, Yotsumoto F, Yagi H, Nakashima M, Watanabe T, Nakano H (2007) Clinical significance of RCAS1 as a biomarker of ovarian cancer. Oncol Rep 17:623–628

    PubMed  CAS  Google Scholar 

  18. Aoe K, Hiraki A, Yamazaki K, Nakamura Y, Murakami T, Maeda T, Nishimura M, Sugi K, Ueoka H (2006) Elevated pleural fluid RCAS1 is a diagnostic marker and outcome predictor in lung cancer patients. Int J Oncol 29:65–72

    PubMed  CAS  Google Scholar 

  19. Jemal A, Siegel E, Ward E, Murray T, Xu J, Smigal C, Thun MJ (2006) Cancer statistics, 2006. CA Cancer J Clin 56:106–130

    PubMed  Google Scholar 

  20. Evans JD, Morton DG, Neoptolemos JP (1997) Chronic pancreatitis and pancreatic carcinoma. Postgrad Med J 73:543–548

    Article  PubMed  CAS  Google Scholar 

  21. Sarkar FH, Banerjee S, Li Y (2006) Pancreatic cancer: pathogenesis, prevention and treatment. Toxicol Appl Pharmacol (in press) (Epub 11 Nov) [PMID: 17174370]

  22. Miyamoto Y, Maitra A, Ghosh B, Zechner U, Argani P, Iacobuzio-Donahue CA, Sriuranpong V, Iso T, Meszoely IM, Wolfe MS, Hruban RH, Ball DW, Schmid RM, Leach SD (2003) Notch mediates TGF-alpha-induced changes in epithelial differentiation during pancreatic tumorigenesis. Cancer Cell 3:564–576

    Article  Google Scholar 

  23. Smit VT, Boot AJ, Smits AM, Fleuren GJ, Cornelisse CJ, Bos JL (1988) KRAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas. Nucleic Acids Res 16:7773–7783

    Article  PubMed  CAS  Google Scholar 

  24. Schutte M, Hruban RH, Hedrick L, Cho KR, Nadasdy GM, Weinstein CL, Bova GS, Isaacs WB, Cairns P, Nawroz H, Sidransky D, Casero RA Jr, Meltzer PS, Hahn SA, Kern SE (1996) DPC4 gene in various tumor types. Cancer Res 56:2527–2530

    PubMed  CAS  Google Scholar 

  25. American Joint Committee on Cancer (2002) AJCC cancer staging manual, 6th edn. Springer, New York

    Google Scholar 

  26. Enjoji M, Nakashima M, Yamaguchi K, Kotoh K, Nakamuta M (2005) Significance of RCAS1 antigen in hepatocellular, cholangiocellular and pancreatic carcinomas. J Gastroenterol Hepatol 20:1143–1148

    Article  PubMed  CAS  Google Scholar 

  27. Iwasaki T, Nakashima M, Watanabe T, Yamamoto S, Inoue Y, Yamanaka H, Matsumura A, Iuchi K, Mori T, Okada M (2000) Expression and prognostic significance in lung cancer of human tumor-associated antigen RCAS1. Int J Cancer 89:488–493

    Article  PubMed  CAS  Google Scholar 

  28. 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 

  29. Oshikiri T, Miyamoto M, Morita T, Fujita M, Miyasaka Y, Senmaru N, Yamada H, Takahashi T, Horita S, Kondo S (2006) Tumor-associated antigen recognized by the 22-1-1 monoclonal antibody encourages colorectal cancer progression under the scanty CD8+ T cells. Clin Cancer Res 12:411–416

    Article  PubMed  CAS  Google Scholar 

  30. Nakabayashi H, Nakashima M, Hara M, Toyonaga S, Yamada SM, Park KC, Shimizu K (2007) Clinico-pathological significance of RCAS1 expression in gliomas: a potential mechanism of tumor immune escape. Cancer Lett 246:182–189

    Article  PubMed  CAS  Google Scholar 

  31. Sonoda K, Miyamoto S, Hirakawa T, Yagi H, Yotsumoto F, Nakashima M, Watanabe T, Nakano H (2005) Invasive potency related to RCAS1 expression in uterine cervical cancer. Gynecol Oncol 99:189–198

    Article  PubMed  CAS  Google Scholar 

  32. Naito A, Narikiyo M, Yamada Y, Ueno M, Kamada K, Hachisuka T, Yoriki R, Mizuno T, Nakajima Y (2005) A clinical and immunohistochemical study on gastrointestinal mesenchymal (GIMT): RCAS1 as a predictor for recurrence of GIMT. Oncol Rep 14:1127–1132

    PubMed  CAS  Google Scholar 

  33. Ozkan H, Akar T, Koklu S, Coban S (2006) Significance of serum receptor-binding cancer antigen (RCAS1) in pancreatic cancer and benign pancreatobiliary diseases. Pancreatology 6:268–272

    Article  PubMed  CAS  Google Scholar 

  34. Suzuoki M, Hida Y, Miyamoto M, Oshikiri T, Hiraoka K, Nakakubo Y, Shinohara T, Itoh T, Okushiba S, Kondo S, Katoh H (2002) RCAS1 expression as a prognostic factor after curative surgery for extrahepatic bile duct carcinoma. Ann Surg Oncol 9:388–393

    Article  PubMed  Google Scholar 

  35. Enjoji M, Nakamuta M, Yamaguchi K, Kotoh K, Morizono S, Arimura E, Fukushima M, Kuniyoshi M, Nakashima M, Tanaka M, Nawata H (2004) RCAS1, a useful serum marker to predict the recurrence of cancer: two cases of cholangiocarcinoma and pancreatic cancer. Dig Dis Sci 49:1654–1656

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Forensic Medicine and Toxicology, Medical School, University of Athens, 75 Mikras Asias St., 11527, Athens, Greece

    Constantinos Giaginis, Apostolos Zarros, Olga Noussia & Stamatios Theocharis

  2. Second Department of Propedeutic Surgery, Laikon Hospital, Medical School, University of Athens, 75, Agiou Thoma St., 11527, Athens, Greece

    Constantinos Giaginis, Demetrios Davides & Gregorios Kouraklis

  3. Department of Pathology, Tzaneio General Hospital, Zanni & Afentouli St., 18536, Piraeus, Greece

    Adamantia Zizi-Serbetzoglou

Authors
  1. Constantinos Giaginis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Demetrios Davides
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Apostolos Zarros
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Olga Noussia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Adamantia Zizi-Serbetzoglou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gregorios Kouraklis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Stamatios Theocharis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stamatios Theocharis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Giaginis, C., Davides, D., Zarros, A. et al. Clinical Significance of Tumor-associated Antigen RCAS1 Expression in Human Pancreatic Ductal Adenocarcinoma. Dig Dis Sci 53, 1728–1734 (2008). https://doi.org/10.1007/s10620-007-0035-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-007-0035-7

Keywords

Search

Navigation