A low frequency of lymph node metastasis in clear-cell renal cell carcinoma is related to low lymphangiogenic activity

Marcella M Baldewijns, Tania Roskams, Vera Ballet, Gert G Van den Eynden, Steven J Van Laere, Ilse Van der Auwera, Evelyne Lerut, Adriaan P De Bruïne, Victor L Thijssen, Peter B Vermeulen, Hein van Poppel

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

OBJECTIVE: To assess ongoing lymphangiogenesis in renal cell carcinoma (RCC) by histomorphometry and by quantifying mRNA expression levels of lymphangiogenesis-related factors.

MATERIALS AND METHODS: Using D2-40 antibody as a lymphatic marker, lymph vessels were counted in tissue sections of 150 clear-cell RCCs (ccRCC) and 61 non-neoplastic controls, using the Chalkley method, which measures the relative lymph vessel area (LVA). Double-staining with Ki67 and D2-40 was used to assess active lymphangiogenesis. In a subset of 25 ccRCCs and nine non-neoplastic controls mRNA expression levels of lymphangiogenic factors were determined by real-time quantitative reverse transcription-polymerase chain reaction.

RESULTS: LVA was higher in normal renal tissue than in both intra- and peri-tumoral LVA (P < 0.001). LVA in the tumour periphery was higher than in the tumour parenchyma (P < 0.001). Lymphatic endothelial cell proliferation (LECP) was identified in 8.2% of the control sections and was higher than the intratumoral LECP fraction (LECP%, 2.6%; P = 0.02) and the peritumoral LECP% (6.5%; P > 0.05). Compared with controls, ccRCC specimens had higher mRNA expression levels of vascular endothelial growth factor (VEGF)-A and VEGF-C, but lower expression levels of VEGF-D and Prox-1 (all P < 0.001).

CONCLUSION: Our results show that there is only limited ongoing lymphangiogenesis in ccRCC. Given that several growth factors stimulate both angiogenesis and lymphangiogenesis, our observation indirectly indicates that haemangiogenesis predominates in ccRCC. This finding might provide better understanding of why ccRCCs prefer haematogenous dissemination to lymphatic spread.

Original languageEnglish
Pages (from-to)1626-31
Number of pages6
JournalBJU International
Volume103
Issue number12
DOIs
Publication statusPublished - Jun 2009

Cite this

Baldewijns, M. M., Roskams, T., Ballet, V., Van den Eynden, G. G., Van Laere, S. J., Van der Auwera, I., ... van Poppel, H. (2009). A low frequency of lymph node metastasis in clear-cell renal cell carcinoma is related to low lymphangiogenic activity. BJU International, 103(12), 1626-31. https://doi.org/10.1111/j.1464-410X.2008.08272.x