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Clinical Value of Immunohistochemically Detected Lymphatic and Vascular Invasions in Clinically Staged Endometrioid Endometrial Cancer
  1. Farhad Alexander-Sefre, FRCS, MRCOG, MD*,
  2. Robert Nibbs, PhD,
  3. Teresa Rafferty, MB, CHB, PhD*,
  4. Ayse Ayhan, MD, PhD,§,
  5. Naveena Singh, MRCPath and
  6. Ian Jacobs, MD, MRCOG
  1. * Department of Gynaecological Oncology, Glasgow Royal Infirmary, Glasgow, United Kingdom;
  2. Cancer Research UK, Beatson Laboratories, Garscube Estate, Glasgow, United Kingdom;
  3. Department of Pathology, Faculty of Medicine, Hacettepe University, Ankara, Turkey;
  4. § Department of Pathology, Seirei Mikatahara Hospital, Hamamatsu, Japan;
  5. Department of Pathology, St Bartholomew's and the Royal London Medical and Dental School, London, United Kingdom; and
  6. Department of Gynecological Oncology, UCL Institute for Women's Health, University College London, London, United Kingdom.
  1. Address correspondence and reprint requests to Farhad Alexander-Sefre, FRCS, MRCOG, MD, Department of Gynaecological Oncology, Glasgow Royal Infirmary, Surgical Block-Ward 24, Castle St, Glasgow, G4 0SF United Kingdom. E-mail: f.alexander.sefre{at}


Background: A novel technique to differentiate lymphatic from vascular invasion and to assess the clinicopathological significance in patients with early endometrial cancer.

Methods: Dual immunohistochemical techniques against pancytokeratin epithelial cell marker (PCK), D6 lymphatic endothelial marker, and CD31 nonspecific endothelial marker were deployed for differentiation. Seventy-seven patients were included with a median follow-up of 161 months. Tumors with positive evidence of lymphovascular space invasion on PCK-CD31 immunohistochemistry and absence of lymphatic space invasion on PCK-D6 were regarded as cases with vascular space invasion only.

Results: Significant association between depth of myometrial invasion, recurrence rate, and hematoxylin and eosin that detected lymphovascular space invasion were noted (P < 0.0001 and P = 0.009, respectively). The 5-year recurrence-free survival was 45% for the group with hematoxylin and eosin evidence of lymphovascular space invasion compared with 89% for the group without (P = 0.0014). Pancytokeratin epithelial cell marker-D6 dual immunostaining detected lymphatic space invasion in 22 (29%) patients. There was significant association between lymphatic space invasion and depth of myometrial invasion (P = 0.046). Lymphatic space invasion detected on immunohistochemistry was present in 8 (72%) of 11 patients with recurrent disease. Of the remaining 49 patients with no evidence of recurrent disease, only 11 (22%) had presented with lymphatic space invasion. Positive association between tumor recurrence rate and lymphatic space invasion was noted (P = 0.003). The 5-year recurrence-free survival was 53% for the group with lymphatic invasion compared with 93% for the group without. This difference was similarly shown to be of significance (P = 0.0009). There were no apparent association between immunohistochemically detected lymphovascular or vascular space invasion and any clinicopathological factor.

Conclusions: Lymphatic space invasion detected by using dual immunostaining is of significant value in identifying high-risk patients.

  • Endometrial cancer
  • D6
  • LVSI
  • Lymphatic invasion

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