ORIGINAL ARTICLE

LYVE-1 immunohistochemical assessment of lymphangiogenesis in endometrial and lung cancer

M I Koukourakis¹, A Giatromanolaki¹, E Sivridis¹, C Simopoulos¹, K C Gatter², A L Harris³ and D G Jackson⁴

¹ Tumour and Angiogenesis Research Group, Departments of Radiotherapy/Oncology, Pathology, and Surgery, Democritus University of Thrace, Medical School, Alexandroupolis 68100, Greece
² Department of Pathology, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford OX3 9DS, UK
³ Cancer Research UK, Molecular Oncology Laboratories, Weatheral Institute of Molecular Medicine, John Radcliffe Hospital
⁴ MRC Human Immunology Unit, Institute of Molecular Medicine, Oxford Radcliffe Hospital, Headington, Oxford OX3 9DS, UK

Correspondence to:
Correspondence to:
Dr M I Koukourakis
Tumour and Angiogenesis Research Group, PO Box 12, Alexandroupolis 68100, Greece; targ{at}her.forthnet.gr

Aims/Methods: Normal and malignant pulmonary and endometrial tissues were analysed for lymphatic vessels to assess the process of lymphangiogenesis and its role at these sites, using specific immunostaining for LYVE-1 and the panendothelial marker CD31.

Results: Lymphatics were clearly demonstrated in some normal tissues (myometrium, bronchial submucosa, and intestinal submucosa), but not in others (endometrium and alveolar tissue). LYVE-1 positive lymphatic vessels were detected at the tumour periphery of endometrial and lung carcinomas, but not within the main tumour mass. Double staining for LYVE-1 and the MIB1 proliferation marker revealed a higher proliferation index in lymphatic endothelial cells at the invading front of endometrial carcinomas, compared with myometrial areas distal to the tumour. Lung and endometrial carcinomas did not have an intratumorous lymphatic network.

Conclusions: Although lymphangiogenesis may occur at the invading tumour front, incorporated lymphatics do not survive. Therefore, the dissemination of cancer cells through the lymphatics may occur by invasion of peripheral cancer cells into the adjacent normal lymphatics, or through shunts eventually produced at the invading tumour front as a consequence of active angiogenesis and lymphangiogenesis.

Abbreviations: APAAP, alkaline phosphatase/antialkaline phosphatase; DAB, diaminobenzidine; MoAb, monoclonal antibody; PBS, phosphate buffered saline; TBS, Tris buffered saline; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor

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