Intratumoral lymphangiogenesis and lymph node metastasis in head and neck cancer.
How tumors access and spread via the lymphatics is not understood. Although it is clear that dissemination via the blood system involves hemangiogenesis, it is uncertain whether tumors also induce lymphangiogenesis or simply invade existing peritumoral vessels. To address the issue we quantitated tumor lymph vessels in archival specimens of head and neck cancer by immunostaining for the recently described lymphatic endothelial marker LYVE-1, the vascular endothelial marker CD34, and the pKi67 proliferation marker, correlating lymph vessel density and proliferation index with clinical and pathological variables. Discrete "hotspots" of intratumoral small proliferating lymphatics were observed in all carcinomas, and a high intratumoral lymph vessel density was associated with neck node metastases (n = 23; P = 0.027) and an infiltrating margin of tumor invasion (P = 0.046) in the oropharyngeal subgroup. Quantitation of the lymphangiogenic growth factor vascular endothelial growth factor C by real-time PCR and immunohistochemistry revealed higher levels of mRNA in tumor tissue than in normal samples (n = 8; P = 0.017), but no obvious correlation with intratumoral lymphatics. Our results provide new evidence that proliferating lymphatics can occur in human cancers and may in some cases contribute to lymph node metastasis.
Beasley
Nigel J P
NJ
Oxford Centre for Head and Neck Oncology, Radcliffe Infirmary, Oxford OX2 6HE, United Kingdom.
Prevo
Remko
R
Banerji
Suneale
S
Leek
Russell D
RD
Moore
John
J
van Trappen
Philippe
P
Cox
Graham
G
Harris
Adrian L
AL
Jackson
David G
DG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002455:Cell Division; D016228:Endothelial Growth Factors / Q000032:analysis; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D008207:Lymphatic Metastasis; D008208:Lymphatic System / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000209:etiology*; D042582:Vascular Endothelial Growth Factor C
D016228:Endothelial Growth Factors; D042582:Vascular Endothelial Growth Factor C