Angiogenesis and the expression of vascular endothelial growth factors A and C in squamous cell carcinoma of the piriform fossa.
BACKGROUND
Angiogenesis is essential for tumor growth and invasion. Vascular endothelial growth factor A (VEGF-A) is a prime mediator of tumor angiogenesis; VEGF-C, another member of the closely related VEGF family of proteins, has major effects on lymphatic endothelial cells and may be important in the process of lymphatic metastasis.


OBJECTIVE
To evaluate the expression of these cytokines in hypopharyngeal squamous cell carcinoma and to ascertain the effects of these proteins on lymphatic metastasis and vascular angiogenesis.


METHODS
Retrospective analysis of microvessel density and the expression of VEGF-A and VEGF-C.


METHODS
An academic referral center. Subjects Thirty-four patients with stage T2 to T4 squamous cell carcinoma of the piriform fossa.


METHODS
Expression of VEGF-A and VEGF-C was determined by immunohistochemistry on formalin-fixed, paraffin-embedded biopsy specimens. Angiogenesis was measured as microvessel density by staining endothelial cells for platelet-endothelial cell adhesion molecule 1/CD31.


RESULTS
Of the 34 tumors, 21 had clinicoradiologic evidence of lymphatic metastasis. Expression of VEGF-C was associated with lymphatic metastasis (P<.001), but not with microvessel density. The VEGF-A expression correlated with microvessel density (P<.001), but neither VEGF-A expression nor microvessel density was associated with lymphatic metastasis.


CONCLUSIONS
The expression of VEGF-C is associated with lymphatic metastasis in squamous cell carcinoma of the piriform fossa. This is not secondary to effects on vascular angiogenesis and is hypothesized to be due to effects on lymphatic endothelial cells.
Department of Otolaryngology-Head and Neck Surgery, Hull Royal Infirmary, Hull, England.
Jarrod J
JJ
Homer
Michael G
MG
Prentice
Lynn
L
Cawkwell
Martin
M
Birchall
John
J
Greenman
Nicholas D
ND
Stafford
D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D005260:Female; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000473:pathology*; D007013:Hypopharynx / Q000098:blood supply* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology*; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*; D042561:Vascular Endothelial Growth Factor B / Q000032:analysis*
D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B