Detection of lymphovascular invasion by D2-40 (podoplanin) immunoexpression in endometrial cancer

Int J Gynecol Cancer. 2012 Oct;22(8):1442-8. doi: 10.1097/IGC.0b013e318269139b.

Abstract

Background: Lymph node involvement is a major feature in tumor spread of endometrial cancer and predicts prognosis. Therefore, evaluation of lymph vessel invasion (LVI) in tumor tissue as a predictor for lymph node metastasis is of great importance. Immunostaining of D2-40 (podoplanin), a specific marker for lymphatic endothelial cells, might be able to increase the detection rate of LVI compared with conventional hematoxylin-eosin (H-E) staining. The aim of this retrospective study was to analyze the eligibility of D2-40-based LVI evaluation for the prediction of lymph node metastases and patients' outcome.

Patients and methods: Immunohistochemical staining with D2-40 monoclonal antibodies was performed on paraffin-embedded tissue sections of 182 patients with primary endometrioid adenocarcinoma treated in 1 gynecologic cancer center. Tumors were screened for the presence of LVI. Correlations with clinicopathological features and clinical outcome were assessed.

Results: Immunostaining of D2-40 significantly increased the frequency LVI detection compared with conventional H-E staining. Lymph vessel invasion was identified by D2-40 in 53 (29.1%) of 182 tumors compared with 34 (18.3%) of 182 carcinomas by routine H-E staining (P = 0.001). D2-40 LVI was detectable in 81.0% (17/21) of nodal-positive tumors and significantly predicted lymph node metastasis (P = 0.001). Furthermore, D2-40 LVI was an independent prognostic factor for patients overall survival considering tumor stage, lymph node involvement, and tumor differentiation (P < 0.01). D2-40-negative tumors confined to the inner half of the myometrium showed an excellent outcome (5-year overall survival, 97.8%).

Conclusions: D2-40-based LVI assessment improves the histopathological detection of lymphovascular invasion in endometrial cancer. Furthermore, LVI is of prognostic value and predicts lymph node metastasis. D2-40 LVI detection might help to select endometrial cancer patients who will benefit from a lymphadenectomy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived / immunology*
  • Biomarkers, Tumor / immunology
  • Biomarkers, Tumor / metabolism*
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / mortality
  • Endometrial Neoplasms / pathology*
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology*
  • Lymphatic Metastasis
  • Lymphatic Vessels / immunology
  • Lymphatic Vessels / metabolism
  • Lymphatic Vessels / pathology*
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism*
  • Middle Aged
  • Myometrium / pathology
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Prognosis
  • Retrospective Studies
  • Survival Rate

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Biomarkers, Tumor
  • Membrane Glycoproteins
  • PDPN protein, human
  • monoclonal antibody D2-40