ORIGINAL ARTICLE

Lack of lymphangiogenesis during breast carcinogenesis

M M Vleugel¹, R Bos¹, P van der Groep¹, A E Greijer¹, A Shvarts¹, H V Stel², E van der Wall³ and P J van Diest⁴

¹ Department of Oncology/Pathology, VU University Medical Centre, 1007 MB Amsterdam, The Netherlands
² Department of Pathology, Hospital Gooi-Noord, 1261 AN Blaricum, The Netherlands
³ Division of Internal Medicine and Dermatology, University Medical Centre Utrecht, 3508 GA Utrecht, The Netherlands
⁴ Department of Pathology, University Medical Centre Utrecht

Correspondence to:
Correspondence to:
Professor P J van Diest
Department of Pathology, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands; p.j.vandiest{at}lab.azu.nl

Background: Recent evidence suggests that functional intratumorous lymph vessels may be absent from some human cancers. This could result from either the failure of tumours to induce lymphangiogenesis, or the collapse of lymph vessels, caused by high interstitial tumour pressure.

Methods: To differentiate between these two hypotheses, paraffin wax embedded clinical specimens from normal breast (n = 13), usual ductal hyperplasia (n = 11), ductal carcinoma in situ (n = 21), and invasive breast cancer (n = 40) were compared for lymphatic and blood vessel density by immunohistochemistry with antibodies to the lymphatic endothelial hyaluronan receptor (LYVE-1) and CD31, respectively.

Results: Lymph vessel density was lower than blood vessel density in normal breast tissue. Within breast lobuli, lymph vessels were absent. In premalignant lesions blood microvessel density increased, whereas no increase in lymph vessels could be seen intralesionally. In invasive cancers, lymph vessels were absent in all but a few cases, where probably some pre-existing lymph vessels remained, although blood microvessel density was once again increased.

Conclusion: Unlike angiogenesis, lymphangiogenesis is absent during breast carcinogenesis. This, and not rising interstitial pressure caused by an increase in the size of lesions, explains the absence of intratumorous lymph vessels in invasive breast cancer.

Abbreviations: BVD, blood vessel density/mm²; DCIS, ductal carcinoma in situ; HNSCC, head and neck squamous cell carcinoma; LVD, lymph vessel density/mm²; NHS, normal human serum; TBS, Tris buffered saline; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor

Keywords: breast; carcinogenesis; lymphangiogenesis; angiogenesis; immunohistochemistry

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