Top

World Journal of Surgery

Published in:

Open Access 01-06-2012

Prognostic Relevance of Survivin in Pancreatic Endocrine Tumors

Authors: Sara Ekeblad, Margareta Halin Lejonklou, Peter Stålberg, Britt Skogseid

Published in: World Journal of Surgery | Issue 6/2012

Abstract

Background

Better prognostic markers are needed for pancreatic endocrine tumors. Survivin is an apoptosis inhibitor that is suggested to have a negative prognostic impact in several tumor types. Contradictory data exist, especially regarding the significance of a nuclear versus cytoplasmic location of survivin. The prognostic relevance of nuclear and cytoplasmic survivin expression in pancreatic endocrine tumors—controlled for the tumor Ki-67 index, World Health Organization classification, and TNM stage—was investigated.

Methods

A total of 111 patients treated at a tertiary referral center were retrospectively evaluated. Clinical data were gathered from medical records. Immunohistochemistry for survivin and Ki-67 was performed on paraffin-embedded tissue. Univariate and multivariate Cox analyses were performed.

Results

Patients with tumors that had <5% survivin-positive nuclei had a mean survival of 225 months [95% confidence interval (CI) 168–281]. The corresponding figure for patients with 5 to 50% survivin-positive tumor cell nuclei was 101 months [95% CI 61–140; hazard ratio (HR) 2.4; P < 0.01) and with >50% survivin-positive nuclei 47 months (95% CI 24–71; HR 4.9; P < 0.001). Nuclear survivin expression in >50% of the tumor cells was an independent marker of a poor prognosis (HR 5.7; P < 0.01). Cytoplasmic survivin was not a significant prognostic factor in the multivariate analysis (HR 0.94; P = 0.90).

Conclusions

High expression of nuclear survivin is a significant marker of a poor prognosis in patients with a pancreatic endocrine tumor.

Hochwald SN, Zee S, Conlon KC et al (2002) Prognostic factors in pancreatic endocrine neoplasms: an analysis of 136 cases with a proposal for low-grade and intermediate-grade groups. J Clin Oncol 20:2633–2642PubMedCrossRef

Tomassetti P, Campana D, Piscitelli L et al (2005) Endocrine pancreatic tumors: factors correlated with survival. Ann Oncol 16:1806–1810PubMedCrossRef

Pape UF, Bohmig M, Berndt U et al (2004) Survival and clinical outcome of patients with neuroendocrine tumors of the gastroenteropancreatic tract in a German referral center. Ann N Y Acad Sci 1014:222–233PubMedCrossRef

Panzuto F, Nasoni S, Falconi M et al (2005) Prognostic factors and survival in endocrine tumor patients: comparison between gastrointestinal and pancreatic localization. Endocr Relat Cancer 12:1083–1092PubMedCrossRef

Kloppel G, Perren A, Heitz PU (2004) The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO classification. Ann N Y Acad Sci 1014:13–27PubMedCrossRef

Pelosi G, Bresaola E, Bogina G et al (1996) Endocrine tumors of the pancreas: Ki-67 immunoreactivity on paraffin sections is an independent predictor for malignancy: a comparative study with proliferating-cell nuclear antigen and progesterone receptor protein immunostaining, mitotic index, and other clinicopathologic variables. Hum Pathol 27:1124–1134PubMedCrossRef

Clarke MR, Baker EE, Weyant RJ et al (1997) Proliferative activity in pancreatic endocrine tumors: association with function, metastases, and survival. Endocr Pathol 8:181–187PubMedCrossRef

La Rosa S, Sessa F, Capella C et al (1996) Prognostic criteria in nonfunctioning pancreatic endocrine tumours. Virchows Arch 429:323–333PubMedCrossRef

Deschamps L, Handra-Luca A, O’Toole D et al (2006) CD10 expression in pancreatic endocrine tumors: correlation with prognostic factors and survival. Hum Pathol 37:802–808PubMedCrossRef

10.

Ekeblad S, Skogseid B, Dunder K et al (2008) Prognostic factors and survival in 324 patients with pancreatic endocrine tumor treated at a single institution. Clin Cancer Res 14:7798–7803PubMedCrossRef

11.

Rindi G, Kloppel G, Alhman H et al (2006) TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch 449:395–401PubMedCrossRef

12.

Fischer L, Kleeff J, Esposito I et al (2008) Clinical outcome and long-term survival in 118 consecutive patients with neuroendocrine tumours of the pancreas. Br J Surg 95:627–635PubMedCrossRef

13.

LaCasse EC, Baird S, Korneluk RG et al (1998) The inhibitors of apoptosis (IAPs) and their emerging role in cancer. Oncogene 17:3247–3259PubMedCrossRef

14.

Deveraux QL, Reed JC (1999) IAP family proteins: suppressors of apoptosis. Genes Dev 13:239–252PubMedCrossRef

15.

Marusawa H, Matsuzawa S, Welsh K et al (2003) HBXIP functions as a cofactor of survivin in apoptosis suppression. EMBO J 22:2729–2740PubMedCrossRef

16.

Altieri DC (2006) The case for survivin as a regulator of microtubule dynamics and cell-death decisions. Curr Opin Cell Biol 18:609–615PubMedCrossRef

17.

Lens SM, Vader G, Medema RH (2006) The case for survivin as mitotic regulator. Curr Opin Cell Biol 18:616–622PubMedCrossRef

18.

Velculescu VE, Madden SL, Zhang L et al (1999) Analysis of human transcriptomes. Nat Genet 23:387–388PubMedCrossRef

19.

Pennati M, Folini M, Zaffaroni N (2008) Targeting survivin in cancer therapy. Expert Opin Ther Targets 12:463–476PubMedCrossRef

20.

Kelly RJ, Lopez-Chavez A, Citrin D et al (2011) Impacting tumor cell-fate by targeting the inhibitor of apoptosis protein survivin. Mol Cancer 10:35PubMedCrossRef

21.

Lu B, Gonzalez A, Massion PP et al (2004) Nuclear survivin as a biomarker for non-small-cell lung cancer. Br J Cancer 91:537–540PubMedCrossRef

22.

Fields AC, Cotsonis G, Sexton D et al (2004) Survivin expression in hepatocellular carcinoma: correlation with proliferation, prognostic parameters, and outcome. Mod Pathol 17:1378–1385PubMedCrossRef

23.

Okada E, Murai Y, Matsui K et al (2001) Survivin expression in tumor cell nuclei is predictive of a favorable prognosis in gastric cancer patients. Cancer Lett 163:109–116PubMedCrossRef

24.

Kennedy SM, O’Driscoll L, Purcell R et al (2003) Prognostic importance of survivin in breast cancer. Br J Cancer 88:1077–1083PubMedCrossRef

25.

Tonini G, Vincenzi B, Santini D et al (2005) Nuclear and cytoplasmic expression of survivin in 67 surgically resected pancreatic cancer patients. Br J Cancer 92:2225–2232PubMedCrossRef

26.

Grabowski P, Griss S, Arnold CN et al (2005) Nuclear survivin is a powerful novel prognostic marker in gastroenteropancreatic neuroendocrine tumor disease. Neuroendocrinology 81:1–9PubMedCrossRef

27.

Mahotka C, Liebmann J, Wenzel M et al (2002) Differential subcellular localization of functionally divergent survivin splice variants. Cell Death Differ 9:1334–1342PubMedCrossRef

28.

Caldas H, Jiang Y, Holloway MP et al (2005) Survivin splice variants regulate the balance between proliferation and cell death. Oncogene 24:1994–2007PubMedCrossRef

29.

Badran A, Yoshida A, Ishikawa K et al (2004) Identification of a novel splice variant of the human anti-apoptopsis gene survivin. Biochem Biophys Res Commun 314:902–907PubMedCrossRef

30.

Noton EA, Colnaghi R, Tate S et al (2006) Molecular analysis of survivin isoforms: evidence that alternatively spliced variants do not play a role in mitosis. J Biol Chem 281:1286–1295PubMedCrossRef

Title: Prognostic Relevance of Survivin in Pancreatic Endocrine Tumors
Authors: Sara Ekeblad
Margareta Halin Lejonklou
Peter Stålberg
Britt Skogseid
Publication date: 01-06-2012
Publisher: Springer-Verlag
Published in: World Journal of Surgery / Issue 6/2012
Print ISSN: 0364-2313
Electronic ISSN: 1432-2323
DOI: https://doi.org/10.1007/s00268-011-1345-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Prognostic Relevance of Survivin in Pancreatic Endocrine Tumors

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 6/2012

Ectopic Hormone-Secreting Pheochromocytoma: A Francophone Observational Study

Adrenalectomy Improves Outcomes of Selected Patients with Metastatic Carcinoma

Postoperative Hungry Bone Syndrome in Patients with Secondary Hyperparathyroidism of Renal Origin

Slit Versus Non-slit Mesh Placement in Total Extraperitoneal Inguinal Hernia Repair: Reply

Preoperative Localizing Studies for Initial Parathyroidectomy in MEN1 Syndrome: Is There Any Benefit?

Not the Number but the Location of Lymph Nodes Matters for Recurrence Rate and Disease-Free Survival in Patients with Differentiated Thyroid Cancer