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Neuron navigator-2 and cyclin D2 are new candidate prognostic markers in uterine sarcoma

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Abstract

The objective of this study was to validate the diagnostic and clinical role of four protein products of genes previously found to be differentially expressed in uterine low-grade endometrial stromal sarcoma (LG-ESS) compared to uterine leiomyosarcoma (LMS). Protein expression by immunohistochemistry of transgelin (TGLN), neuron navigator-2 (NAV2), fatty acid binding protein-3 (FABP3), and cyclin D2 (CCND2) was analyzed in 305 uterine sarcomas (231 LMS, 74 LG-ESS). Expression was analyzed for association with clinicopathologic parameters and survival. TGLN (p < 0.001), NAV2 (p < 0.001), and FABP3 (p = 0.005) were overexpressed in LMS compared to LG-ESS, whereas nuclear CCND2 (p < 0.001) was overexpressed in LG-ESS. NAV2 expression was associated with shorter overall survival in patients with LMS (p = 0.037), whereas nuclear CCND2 expression in LG-ESS was significantly related to longer survival (p = 0.012) in univariate analysis. Nuclear CCND2 expression was an independent prognosticator in Cox multivariate analysis (p = 0.023). In conclusion, TGLN, FABP3, NAV2, and nuclear CCND2 aid in differentiating LG-ESS from LMS. NAV2 and CCND2 are novel candidate prognostic markers in LMS and LG-ESS, respectively.

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References

  1. Toro JR, Travis LB, Wu HJ et al (2006) Incidence patterns of soft tissue sarcomas, regardless of primary site, in the surveillance, epidemiology and end results program, 1978-2001: an analysis of 26,758 cases. Int J Cancer 119:2922–2930

    Article  CAS  PubMed  Google Scholar 

  2. D'Angelo E, Prat J (2010) Uterine sarcomas: a review. Gynecol Oncol 116:131–139

    Article  PubMed  Google Scholar 

  3. Kurman RJ, Carcangiu ML, Herrington CS et al (2014) WHO classification of tumours of female reproductive organs. IARC, Lyon, France

    Google Scholar 

  4. Veras E, Zivanovic O, Jacks L et al (2011) “Low-grade leiomyosarcoma” and late-recurring smooth muscle tumors of the uterus: a heterogenous collection of frequently misdiagnosed tumors associated with an overall favorable prognosis relative to conventional uterine leiomyosarcomas. Am J Surg Pathol 35:1626–1637

    Article  PubMed  Google Scholar 

  5. Oliva E, Young RH, Amin MB et al (2002) An immunohistochemical analysis of endometrial stromal and smooth muscle tumors of the uterus: a study of 54 cases emphasizing the importance of using a panel because of overlap in immunoreactivity for individual antibodies. Am J Surg Pathol 26:403–412

    Article  PubMed  Google Scholar 

  6. Abeler VM, Nenodovic M (2011) Diagnostic immunohistochemistry in uterine sarcomas: a study of 397 cases. Int J Gynecol Pathol 30:236–243

    Article  PubMed  Google Scholar 

  7. Davidson B, Abeler VM, Hellesylt E et al (2013) Gene expression signatures differentiate uterine endometrial stromal sarcoma from leiomyosarcoma. Gynecol Oncol 128:349–355

    Article  CAS  PubMed  Google Scholar 

  8. Abeler VM, Røyne O, Thoresen S et al (2009) Uterine sarcomas in Norway. A histopathological and prognostic survey of a total population from 1970 to 2000 including 419 patients. Histopathology 54:355–364

    Article  PubMed  Google Scholar 

  9. Musgrove EA, Caldon CE, Barraclough J et al (2011) Cyclin D as a therapeutic target in cancer. Nat Rev Cancer 11:558–572

    Article  CAS  PubMed  Google Scholar 

  10. Assinder SJ, Stanton JA, Prasad PD (2009) Transgelin: an actin-binding protein and tumour suppressor. Int J Biochem Cell Biol 41:482–486

    Article  CAS  PubMed  Google Scholar 

  11. Storch J, McDermott L (2009) Structural and functional analysis of fatty acid-binding proteins. J Lipid Res 50(Suppl):S126–S131

    Article  PubMed  PubMed Central  Google Scholar 

  12. McNeill EM, Klöckner-Bormann M, Roesler EC et al (2011) Nav2 hypomorphic mutant mice are ataxic and exhibit abnormalities in cerebellar development. Dev Biol 353:331–343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. McNeill EM, Roos KP, Moechars D et al (2010) Nav2 is necessary for cranial nerve development and blood pressure regulation. Neural Dev 5:6

    Article  PubMed  PubMed Central  Google Scholar 

  14. Cancer Genome Atlas Network (2012) Comprehensive molecular charactserization of human colon and rectal cancer. Nature 487:330–337

    Article  Google Scholar 

  15. Robin YM, Penel N, Pérot G et al (2013) Transgelin is a novel marker of smooth muscle differentiation that improves diagnostic accuracy of leiomyosarcomas: a comparative immunohistochemical reappraisal of myogenic markers in 900 soft tissue tumors. Mod Pathol 26:502–510

    Article  CAS  PubMed  Google Scholar 

  16. Tawfik O, Rao D, Nothnick WB et al (2014) Transgelin, a novel marker of smooth muscle differentiation, effectively distinguishes endometrial stromal tumors from uterine smooth muscle tumors. Int J Gynecol Obstet Reprod Med Res 1:26–31

    PubMed  PubMed Central  Google Scholar 

  17. Hwang H, Matsuo K, Duncan K et al (2015) Immunohistochemical panel to differentiate endometrial stromal sarcoma, uterine leiomyosarcoma and leiomyoma: something old and something new. J Clin Pathol 68:710–717

    Article  CAS  PubMed  Google Scholar 

  18. Tan F, Zhu H, Tao Y et al (2015) Neuron navigator 2 overexpression indicates poor prognosis of colorectal cancer and promotes invasion through the SSH1L/cofilin-1 pathway. J Exp Clin Cancer Res 34:117

    Article  PubMed  PubMed Central  Google Scholar 

  19. Tang Z, Shen Q, Xie H et al (2016) Elevated expression of FABP3 and FABP4 cooperatively correlates with poor prognosis in non-small cell lung cancer (NSCLC). Oncotarget 7:46253–46262

    Article  PubMed  PubMed Central  Google Scholar 

  20. Takano Y, Kato Y, Masuda M et al (1999) Cyclin D2, but not cyclin D1, overexpression closely correlates with gastric cancer progression and prognosis. J Pathol 189:194–200

    Article  CAS  PubMed  Google Scholar 

  21. Rao D, Kimler BF, Nothnick WB et al (2015) Transgelin: a potentially useful diagnostic marker differentially expressed in triple-negative and non-triple-negative breast cancers. Hum Pathol 46:876–883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lin Y, Buckhaults PJ, Lee JR et al (2009) Association of the actin-binding protein transgelin with lymph node metastasis in human colorectal cancer. Neoplasia 11:864–873

    Article  PubMed  PubMed Central  Google Scholar 

  23. Zhou L, Zhang R, Zhang L et al (2013) Upregulation of transgelin is an independent factor predictive of poor prognosis in patients with advanced pancreatic cancer. Cancer Sci 104:423–430

    Article  CAS  PubMed  Google Scholar 

  24. Zhao L, Wang H, Deng YJ et al (2009) Transgelin as a suppressor is associated with poor prognosis in colorectal carcinoma patients. Mod Pathol 22:786–796

    CAS  PubMed  Google Scholar 

  25. Pérot G, Mendiboure J, Brouste V et al (2014) Smooth muscle differentiation identifies two classes of poorly differentiated pleomorphic sarcomas with distinct outcome. Mod Pathol 27:840–850

    Article  PubMed  Google Scholar 

  26. Davidson B, Kjæreng ML, Førsund M et al (2016) Progesterone receptor expression is an independent prognosticator in FIGO stage I uterine leiomyosarcoma. Am J Clin Pathol 145:449–458

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by a grant from the National Sarcoma Foundation at the Norwegian Radium Hospital.

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Correspondence to Ben Davidson.

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The authors declare that they have no conflict of interest.

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The study was approved by the regional committee for medical research ethics in Norway.

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Davidson, B., Hellesylt, E., Holth, A. et al. Neuron navigator-2 and cyclin D2 are new candidate prognostic markers in uterine sarcoma. Virchows Arch 471, 355–362 (2017). https://doi.org/10.1007/s00428-017-2172-5

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  • DOI: https://doi.org/10.1007/s00428-017-2172-5

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