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

Virchows Arch. 2017 Sep;471(3):355-362. doi: 10.1007/s00428-017-2172-5. Epub 2017 Jun 22.


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.

Keywords: Diagnosis; Immunohistochemistry; Survival; Uterine sarcoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Cyclin D2 / biosynthesis*
  • DNA Helicases
  • Diagnosis, Differential
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Leiomyosarcoma / diagnosis*
  • Leiomyosarcoma / mortality
  • Leiomyosarcoma / pathology
  • Middle Aged
  • Nerve Tissue Proteins / biosynthesis*
  • Prognosis
  • Sarcoma, Endometrial Stromal / diagnosis*
  • Sarcoma, Endometrial Stromal / mortality
  • Sarcoma, Endometrial Stromal / pathology
  • Uterine Neoplasms / diagnosis*
  • Uterine Neoplasms / mortality
  • Uterine Neoplasms / pathology
  • Young Adult


  • Biomarkers, Tumor
  • CCND2 protein, human
  • Cyclin D2
  • Nerve Tissue Proteins
  • DNA Helicases
  • NAV2 protein, human