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Original Paper

Nuclear Survivin Is a Powerful Novel Prognostic Marker in Gastroenteropancreatic Neuroendocrine Tumor Disease

Grabowski P.a · Griβ S.a · Arnold C.N.d · Hörsch D.c · Göke R.c · Arnold R.c · Heine B.b · Stein H.b · Zeitz M.a · Scherübl H.a

Author affiliations

aMedical Clinic I, Gastroenterology/Infectious Diseases/Rheumatology; bInstitute of Pathology, Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin; cDepartment of Internal Medicine, Division of Gastroenterology and Endocrinology, Philipps University Marburg, Marburg, and dDepartment of Medicine II, University of Freiburg, Freiburg, Germany

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Neuroendocrinology 2005;81:1–9

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: August 26, 2004
Accepted: January 18, 2005
Published online: May 26, 2005
Issue release date: May 2005

Number of Print Pages: 9
Number of Figures: 5
Number of Tables: 2

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: https://www.karger.com/NEN

Abstract

Gastroenteropancreatic neuroendocrine tumors represent a heterogeneous tumor entity. The growth pattern ranges from very slowly to fast growing, aggressive types of tumors. Survivin, a member of the family of apoptosis inhibitors, is a bifunctional protein that suppresses apoptosis and regulates cell division. In this study we determined the prognostic value of survivin in this tumor entity. Tumor specimens from 104 patients (38 foregut, 53 midgut, 13 hindgut) were studied immunohistochemically for cytoplasmic and nuclear survivin expression as well as for ki-67 antigen expression. 5-year-follow-up was complete in 89 patients. 29 patients with localized, well-differentiated gastroenteropancreatic neuroendocrine tumors (WDET, WHO class 1) had been curatively treated by surgical or endoscopic tumor resection. 50 patients suffered from well-differentiated endocrine carcinomas (WDEC, WHO class 2), 10 patients were diagnosed with poorly differentiated neuroendocrine carcinomas (PDEC, WHO class 3). Survivin expression was correlated with survival for the 50 patients with metastatic WDEC disease. All 29 WDETs were negative for nuclear survivin, whereas all 10 PDECs stained positive for nuclear survivin. In the 50 patients with metastatic WDECs, 5/50 (10%) tumors were nuclear survivin positive. Those 5 patients had a statistically significant worse prognosis (survival of 41 vs. 103 months, p = 0.01). ki-67 was not a prognostic factor in this subgroup of patients. Nuclear survivin expression thus appears to be upregulated during progression of gastroenteropancreatic neuroendocrine tumors. The analysis of nuclear survivin expression identifies subgroups in metastatic disease (WHO class 2) with good (survivin) or with less favorable prognosis (survivin+). We propose that the determination of nuclear survivin expression could be used to individualize therapeutic strategies in this tumor entity in the future.

© 2005 S. Karger AG, Basel


References

  1. Williams ED, Sandler M: The classification of carcinoid tumors. Lancet 1963;i:238–239.
  2. Solcia E, Klöppel G, Sobin LH: WHO International Histological Classification of Tumors. Histological Typing of Endocrine Tumors, ed 2. Berlin, Springer, 2000.
  3. Van Eeden S, Quaedvlieg PF, Taal BG, Offerhaus GJ, Lamers CB, Van Velthuysen ML: Classification of low-grade neuroendocrine tumors of midgut and unknown origin. Hum Pathol 2002;33:1126–1132.
  4. Onaitis MW, Kirshbom PM, Hayward TZ, Quayle FJ, Feldman JM, Seigler HF, Tyler DS: Gastrointestinal carcinoids: Characterization by site of origin and hormone production. Ann Surg 2000;232:549–556.
  5. Moyana TN, Xiang J, Senthilselvan A, Kulaga A: The spectrum of neuroendocrine differentiation among gastrointestinal carcinoids: Importance of histologic grading, MIB-1, p53, and bcl-2 immunoreactivity. Arch Pathol Lab Med 2000;124:570–576.
  6. Altieri DC: Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene 2003;22:8581–8589.
  7. Velculescu VE, Madden SL, Zhang L, et al: Analysis of human transcriptomes. Nat Genet 1999;23:387–388.
  8. Ambrosini G, Adida C, Altieri DC: A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 1997;3:917–921.
  9. Grabowski P, Kühnel T, Mühr-Wilkenshoff F, Heine B, Stein H, Höpfner M, Germer CT, Scherübl H: Prognostic value of nuclear survivin expression in oesophageal squamous cell carcinoma. Br J Cancer 2003;88:115–119.
  10. Kawasaki H, Altieri DC, Lu CD, Toyoda M, Tenjo T, Tanigawa N: Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. Cancer Res 1998;58:5071–5074.
  11. Monzo M, Rosell R, Felip E, Astudillo J, Sanchez JJ, Maestre J, Martin C, Font A, Barnadas A, Abad A: A novel anti-apoptosis gene: Re-expression of survivin messenger RNA as a prognosis marker in non-small-cell lung cancers. J Clin Oncol 1999;17:2100–2104.
  12. Tanaka K, Iwamoto S, Gon G, Nohara T, Iwamoto M, Tanigawa N: Expression of survivin and its relationship to loss of apoptosis in breast carcinomas. Clin Cancer Res 2000;6:127–134.
  13. Adida C, Berrebi D, Peuchmaur M, Reyes-Mugica M, Altieri DC: Anti-apoptosis gene, survivin, and prognosis of neuroblastoma. Lancet 1998;351:882–883.
  14. Kennedy SM, O’Driscoll L, Purcell R, Fitz-Simons N, McDermott EW, Hill AD, O’Higgins NJ, Parkinson M, Linehan R, Clynes M: Prognostic importance of survivin in breast cancer. Br J Cancer 2003;88:1077–1083.
  15. Okada E, Murai Y, Matsui K, Isizawa S, Cheng C, Masuda M, Takano Y: Survivin expression in tumor cell nuclei is predictive of a favorable prognosis in gastric cancer patients. Cancer Lett 2001;163:109–116.
  16. Li F, Ackermann EJ, Bennett CF, Rothermel AL, Plescia J, Tognin S, Villa A, Marchisio PC, Altieri DC: Pleiotropic cell-division defects and apoptosis induced by interference with survivin function. Nat Cell Biol 1999;1:461–466.
  17. Li F, Ambrosini G, Chu EY, Plescia J, Tognin S, Marchisio PC, Altieri DC: Control of apoptosis and mitotic spindle checkpoint by survivin. Nature 1998;396:580–584.
  18. Skoufias DA, Mollinari C, Lacroix FB, Margolis RL: Human survivin is a kinetochore-associated passenger protein. J Cell Biol 2000;151:1575–1582.
  19. Conway EM, Pollefeyt S, Steiner-Mosonyi M, Luo W, Devriese A, Lupu F, Bono F, Leducq N, Dol F, Schaeffer P, Collen D, Herbert JM: Deficiency of survivin in transgenic mice exacerbates Fas-induced apoptosis via mitochondrial pathways. Gastroenterology 2002;123:619–631.
  20. Suzuki A, Hayashida M, Ito T, Kawano H, Nakano T, Miura M, Akahane K, Shiraki K: Survivin initiates cell cycle entry by the competitive interaction with Cdk4/p16(INK4a) and Cdk2/cyclin E complex activation. Oncogene 2000;19:3225–3234.
  21. Suzuki A, Ito T, Kawano H, Hayashida M, Hayasaki Y, Tsutomi Y, Akahane K, Nakano T, Miura M, Shiraki K: Survivin initiates procaspase 3/p21 complex formation as a result of interaction with Cdk4 to resist Fas-mediated cell death. Oncogene 2000;19:1346–1353.
  22. Mirza A, McGuirk M, Hockenberry TN, Wu Q, Ashar H, Black S, Wen SF, Wang L, Kirschmeier P, Bishop WR, Nielsen LL, Pickett CB, Liu S: Human survivin is negatively regulated by wild-type p53 and participates in p53-dependent apoptotic pathway. Oncogene 2002;21:2613–2622.
  23. Grossman D, Kim PJ, Blanc-Brude OP, Brash DE, Tognin S, Marchisio PC, Altieri DC: Transgenic expression of survivin in keratinocytes counteracts UVB-induced apoptosis and cooperates with loss of p53. J Clin Invest 2001;108:991–999.
  24. Grabowski P, Schindler I, Anagnostopoulos I, Foss HD, Riecken EO, Mansmann U, Stein H, Berger G, Buhr HJ, Scherübl H: Neuroendocrine differentiation is a relevant prognostic factor in stage III-IV colorectal cancer. Eur J Gastroenterol Hepatol 2001;13:405–411.
  25. Koch CA, Vortmeyer AO, Diallo R, Poremba C, Giordano TJ, Sanders D, Bornstein SR, Chrousos GP, Pacak K: Survivin: A novel neuroendocrine marker for pheochromocytoma. Eur J Endocrinol 2002;146:381–388.
  26. Xing N, Qian J, Bostwick D, Bergstralh E, Young CY: Neuroendocrine cells in human prostate over-express the anti-apoptosis protein survivin. Prostate 2001;48:7–15.
  27. Gianani R, Jarboe E, Orlicky D, Frost M, Bobak J, Lehner R, Shroyer KR: Expression of survivin in normal, hyperplastic, and neoplastic colonic mucosa. Hum Pathol 2001;32:119–125.
  28. Endl E, Gerdes J: The Ki-67 protein: fascinating forms and an unknown function. Exp Cell Res 2000;257:231–237.
  29. Rindi G, Azzoni C, La Rosa S, Klersy C, Paolotti D, Rappel S, Stolte M, Capella C, Bordi C, Solcia E: ECL cell tumor and poorly differentiated endocrine carcinoma of the stomach: prognostic evaluation by pathological analysis. Gastroenterology 1999;116:532–542.
  30. Mahotka C, Liebmann J, Wenzel M, Suschek CV, Schmitt M, Gabbert HE, Gerharz CD: Differential subcellular localization of functionally divergent survivin splice variants. Cell Death Differ 2002;9:1334–1342.
  31. Krieg A, Mahotka C, Krieg T, Grabsch H, Muller W, Takeno S, Suschek CV, Heydthausen M, Gabbert HE, Gerharz CD: Expression of different survivin variants in gastric carcinomas: First clues to a role of survivin-2B in tumour progression. Br J Cancer 2002;86:737–743.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: August 26, 2004
Accepted: January 18, 2005
Published online: May 26, 2005
Issue release date: May 2005

Number of Print Pages: 9
Number of Figures: 5
Number of Tables: 2

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: https://www.karger.com/NEN


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