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A low frequency of lymph node metastasis in clear‐cell renal cell carcinoma is related to low lymphangiogenic activity
Author(s) -
Baldewijns Marcella M.,
Roskams Tania,
Ballet Vera,
Van den Eynden Gert G.,
Van Laere Steven J.,
Van der Auwera Ilse,
Lerut Evelyne,
De Bruïne Adriaan P.,
Thijssen Victor L.,
Vermeulen Peter B.,
Van Poppel Hein
Publication year - 2009
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2008.08272.x
Subject(s) - lymphangiogenesis , lymphatic system , pathology , angiogenesis , lymphatic vessel , renal cell carcinoma , vascular endothelial growth factor c , medicine , lymph , lymph node , vascular endothelial growth factor , clear cell renal cell carcinoma , metastasis , cancer research , vascular endothelial growth factor a , cancer , vegf receptors
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.