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Stathmin Expression in Pheochromocytomas, Paragangliomas, and in other Endocrine Tumors

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Abstract

Pheochromocytomas are neuroendocrine tumors confined to the adrenal glands, and malignant pheochromocytomas can spread to various sites including the liver, lung, and bones. Paragangliomas occur in numerous locations in the body, so assessment of metastatic disease is more challenging, as patients with familial syndromes often have multiple, possibly independent paragangliomas. The most reliable criterion for malignancy in pheochromocytomas and paragangliomas is metastatic disease. Because there are few immunohistochemical markers that are useful in the diagnosis of malignancy in pheochromocytomas and paragangliomas before they metastasize, more markers are needed to characterize these tumors. Stathmin is a widely expressed 17-kDa cytoplasmic, microtubule destabilizing and sequestering phosphoprotein that is important in cell motility and cancer cell metastasis. It is upregulated in various malignancies. We examined stathmin expression in tissues from patients with pheochromocytomas (n = 48), malignant pheochromocytomas (n = 28), paragangliomas (n = 42), and malignant paragangliomas (n = 21) by immunohistochemistry using tissue microarrays (TMA) with a polyclonal antibody against stathmin. A series of other endocrine tissues and tumors (n = 70) were also examined for stathmin expression. Stathmin was more highly expressed in pheochromocytomas compared to normal adrenals, a finding confirmed by Western blot. There was higher expression of stathmin by immunohistochemical staining in malignant pheochromocytomas compared to pheochromocytomas without metastasis when analyzed by maximal staining (p = 0.012). Stathmin was present in a wide variety of endocrine tumors and was most highly expressed in rapidly proliferating tumors including anaplastic thyroid carcinomas, Merkel cell carcinomas of the skin and small cell carcinomas of the lung. These results show that stathmin is expressed at higher levels in more rapidly proliferating endocrine tumors. However, it is probably not useful as a stand-alone marker to determine malignancy in pheochromocytomas for individual tumors.

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References

  1. Chrisoulidou A, Kaltsas G, Ilias I, et al. The diagnosis and management of malignant phaeochromocytoma and paragangliomas. Endocrine Relat Cancer. 14:569–85, 2007.

    Article  CAS  Google Scholar 

  2. Brouwers FM, Eisenhofer G, Tao JJ, et al. High frequency of SDHB germline mutations in patients with malignant catecholamine-producing paragangliomas: Implications for genetic testing. J Clin Endocrinol Metab. 91:4505–9, 2006.

    Article  PubMed  CAS  Google Scholar 

  3. Neumann HPH, Pawlu C, Peczkowska M, et al. Distinct clinical features of paragangliomas syndromes associated with SDHB and SDHD gene mutations. JAMA. 292:943–51, 2004.

    Article  PubMed  CAS  Google Scholar 

  4. Madani R, Al-Hashmi M, Bliss R, et al. Ectopic pheochromocytoma: does the rule of tens apply? World J Surg. 31:849–54, 2007.

    Article  PubMed  CAS  Google Scholar 

  5. O’Riordain DS, Young WF, Grant CS, et al. Clinical spectrum and outcome of functional extraadrenal paragangliomas. World J Surg. 20:916–22, 1996.

    Article  PubMed  CAS  Google Scholar 

  6. Scott HW, Halter SA. Oncologic aspects of phaeochromocytoma: the importance of follow-up. Surgery. 96:1061–6, 1984.

    PubMed  Google Scholar 

  7. Anouar Y, Yon L, Guillemot J, et al. Development of novel tools for the diagnosis and prognosis of pheochromocytoma using peptide marker immunoassay and gene expression profiling approaches. Ann N Y Acad Sci. 1073:533–40, 2006.

    Article  PubMed  Google Scholar 

  8. Brouwers FM, Elkahloun AG, Munson PJ, et al. Gene expression profiling of benign and malignant pheochromocytoma. Ann N Y Acad Sci. 1073:541–56, 2006.

    Article  PubMed  CAS  Google Scholar 

  9. Thouennon E, Elkahloun AG, Guillemot J, et al. Identification of potential gene markers and insights into the pathophysiology of pheochromocytoma malignancy. J Clin Endocrinol Metab. 92:4865–72, 2007.

    Article  PubMed  CAS  Google Scholar 

  10. Onda M, Emi M, Yoshida A, et al. Comprehensive gene expression profiling of anaplastic thyroid cancers with cDNA microarrays of 25,344 genes. Endocr Relat Cancer. 11:843–54, 2004.

    Article  PubMed  CAS  Google Scholar 

  11. Doye V, Bouttenin M-C, Sobel A. Phosphorylation of stathmin and other proteins related to nerve growth factor—induced regulation of PC12 cells. J Biol Chem. 265:11650–5, 1990.

    PubMed  CAS  Google Scholar 

  12. Takekoshi K, Nomura F, Isobe K, et al. Identification of initial characterization of stathmin by the differential display method in nerve growth factor—treated PC 12 cells. Eur J Endocrinol. 138:707–12, 1998.

    Article  PubMed  CAS  Google Scholar 

  13. Beilharz EJ, Zhukovshy E, Lanahan AA, et al. Neuronal activity induction of the stathmin-like gene RB3 in the rat hippocampus: possible role in neuronal plasticity. J Neurosci. 18:9780–9, 1998.

    PubMed  CAS  Google Scholar 

  14. Steinmetz MO. Structure and thermodynamics of the tubulin–stathmin interaction. J Struct Biol. 158:137–47, 2007.

    Article  PubMed  CAS  Google Scholar 

  15. Rubin CI, Atweh GF. The role of stathmin in the regulation of the cell cycle. J Cell Biochem. 93:242–50, 2004.

    Article  PubMed  CAS  Google Scholar 

  16. Iancu-Rubin C, Atweh GF. p27(Kip1) and stathmin share the stage for the first time. Trends Cell Biol. 15:346–8, 2005.

    Article  PubMed  CAS  Google Scholar 

  17. Cassimeris L. Regulation of microtubule dynamic instability. Cell Motil Cytoskelet. 26(4):275–81, 1993.

    Article  CAS  Google Scholar 

  18. Nogales E. A structural view of microtubule dynamics. Cell Mol Life Sci. 56:133–42, 1999.

    Article  PubMed  CAS  Google Scholar 

  19. Cassimeris L. The oncoprotein 18/stathmin family of microtubule destabilizers. Curr Opin Cell Biol. 14:18–24, 2002.

    Article  PubMed  CAS  Google Scholar 

  20. Hanash S, Strahler JR, Kuick R, et al. Identification of a polypeptide associated with the malignant phenotype in acute leukemia. J Biol Chem. 263:12813–5, 1988.

    PubMed  CAS  Google Scholar 

  21. Friedrich B, Gronberg H, Landstrom M, et al. Differentiation-stage specific expression of oncoprotein 18 in human and rat prostatic adenocarcinoma. Prostate. 27:102–9, 1995.

    Article  PubMed  CAS  Google Scholar 

  22. Golouh R, Cufer T, Sadikov A, et al. The prognostic value of Stathmin-1, S100A2, and SYK proteins in ER-positive primary breast cancer patients treated with adjuvant tamoxifen monotherapy: an immunohistochemical study. Breast Cancer Res Treat. DOI 10.1007/s10549-007-9724-3.

  23. Kononen J, Bubendorf L, Kallioniemi A, et al. Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med. 4:844–7, 1998.

    Article  PubMed  CAS  Google Scholar 

  24. Rumilla KM, Erickson LA, Erickson AK, et al. Galectin-4 expression in carcinoid tumors. Endocr Pathol. 17:243–9, 2006.

    Article  PubMed  CAS  Google Scholar 

  25. Riss D, Jin L, Qian X, et al. Differential expression of galactin-3 in pituitary tumors. Cancer Res. 63:2251–8, 2003.

    PubMed  CAS  Google Scholar 

  26. Lloyd RV, Jin L, Qian X, et al. Aberrant p27kip1 expression in endocrine and other tumors. Am J Pathol. 150:401–7, 1997.

    PubMed  CAS  Google Scholar 

  27. Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 227:680–5, 1970.

    Article  PubMed  CAS  Google Scholar 

  28. DeLellis RA, Lloyd RV, Heitz PV, et al. Tumors of endocrine organs. World Health Organization Classification of Tumors. Lyon: IARC Press, 2004.

    Google Scholar 

  29. Lee S, Nakamura E, Yang H, et al. Neuronal apoptosis linked to EglN3 prolyl hydroxylase and familial pheochromocytoma genes: developmental culling and cancer. Cancer Cell. 8:155–67, 2005.

    Article  PubMed  Google Scholar 

  30. Perren A, Komminoth P. Familial pheochromocytomas and paragangliomas: stories from the sign-out room. Endocr Pathol. 17:337–44, 2006.

    Article  PubMed  CAS  Google Scholar 

  31. Tischler AS. Molecular and cellular biology of pheochromocytomas and extra-adrenal paragangliomas. Endocr Pathol. 17:321–8, 2006.

    Article  PubMed  CAS  Google Scholar 

  32. Benn DE, Gimenez-Roqueplo AP, Reilly JR, et al. Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes. J Clin Endocrinol Metab. 91:827–36, 2006.

    Article  PubMed  CAS  Google Scholar 

  33. Klein RD, Jin L, Rumilla K, et al. Germline SDHB mutations are common in patients with apparently sporadic sympathetic paragangliomas. Diagn Mol Pathol. 2008, March 28 [Epub ahead of print].

  34. Baldassarre G, Belletti B, Nocoloso MS, et al. p27(Kip1)–stathmin interaction influences sarcoma cell migration and invasion. Cancer Cells. 7:51–63, 2005.

    Article  CAS  Google Scholar 

  35. Garrett S, Kapoor TM. Microtubule assembly: catastrophe factors to the rescue. Cancer Biol. 13:R910–2, 2003.

    Google Scholar 

  36. Niethammer P, Bastiaens P, Karsenti E. Stathmin–tubulin interaction gradients in motile and mitotic cells. Science. 303:1862–6, 2004.

    Article  PubMed  CAS  Google Scholar 

  37. McAllister SS, Becker-Hapak M, Pintucci G, et al. Novel p27(kip1) C-terminal scatter domain mediates Rac-dependent cell migration independent of cell cycle arrest functions. Mol Cell Biol. 23:216–28, 2003.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

Thanks to Christine Lohse for help with statistical analysis.

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Authors and Affiliations

  1. Department of Pathology, Brigham and Women’s Hospital, Boston, MA, 02115, USA

    Peter M. Sadow

  2. Department of Laboratory Medicine and Pathology, Mayo Clinic, Hilton 11, 200 First Street SW, Rochester, MN, 55905, USA

    Kandelaria M. Rumilla, Lori A. Erickson & Ricardo V. Lloyd

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  1. Peter M. Sadow
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  2. Kandelaria M. Rumilla
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  3. Lori A. Erickson
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  4. Ricardo V. Lloyd
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Correspondence to Ricardo V. Lloyd.

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Responsible editor: R. V. Lloyd MD, PhD

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Sadow, P.M., Rumilla, K.M., Erickson, L.A. et al. Stathmin Expression in Pheochromocytomas, Paragangliomas, and in other Endocrine Tumors. Endocr Pathol 19, 97–103 (2008). https://doi.org/10.1007/s12022-008-9028-0

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  • DOI: https://doi.org/10.1007/s12022-008-9028-0

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