Title
A low frequency of lymph node metastasis in clear-cell renal cell carcinoma is related to low lymphangiogenic activity A low frequency of lymph node metastasis in clear-cell renal cell carcinoma is related to low lymphangiogenic activity
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Oxford ,
Subject
Human medicine
Source (journal)
BJU international / British Association of Urological Surgeons. - Oxford, 1999, currens
Volume/pages
103(2009) :12 , p. 1626-1631
ISSN
1464-4096
ISI
000266450600006
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
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.
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