Intratumoral microvessel density predicts local treatment failure of radically irradiated squamous cell cancer of the oropharynx.
OBJECTIVE
To determine the predictive value of intratumoral microvessel density (IMD), and of the expression of p53, vascular endothelial growth factor (VEGF) and thrombospondin-1 (TSP-1) for the radiocurability of patients with squamous cell cancer of the oropharynx.


METHODS
139 patients with squamous cell cancer of the oropharynx were radically irradiated (median dose, 74 Gy) between 1991 and 1997. Biopsies from 100 patients were processed for immunohistochemistry. IMD was determined in hot spot areas of tissue stained with anti-CD31 at a magnification of x200. Staining for p53 was considered positive if more than 10% of the cell nuclei overexpressed the protein. Immunostaining of VEGF and TSP-1 was assessed semiquantitatively.


RESULTS
Increasing IMD (range, 54-282) was strongly correlated with incomplete remission of both the primary tumors (p = 0.01) and lymph node metastases (p = 0.02). Moreover, multivariate Cox regression analysis revealed local failure-free survival to decline with increasing IMD (IMD continuous: risk ratio = 1.01 per increase of 1 microvessel, p = 0. 0001; IMD categorical: </= 80: baseline, 81-110: risk ratio = 2.71, 111-130: risk ratio = 4.55, > 130: risk ratio = 13.01). Neither the expression of p53, nor that of VEGF or TSP-1 was associated with the treatment outcome or IMD, but VEGF and TSP-1 expression were positively correlated (p = 0.02).


CONCLUSIONS
IMD represents a powerful and independent predictive factor for local treatment failure in radically irradiated patients with squamous cell cancer of the oropharynx.
Department of Radiation Oncology, University of Berne, Inselspital, Berne, Switzerland.
D M
DM
Aebersold
K T
KT
Beer
J
J
Laissue
S
S
Hug
A
A
Kollar
R H
RH
Greiner
V
V
Djonov
D000704:Analysis of Variance; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000532:radiotherapy*; D005500:Follow-Up Studies; D006801:Humans; D008833:Microcirculation; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000473:pathology*; D009959:Oropharyngeal Neoplasms / Q000098:blood supply* / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D012044:Regression Analysis; D012189:Retrospective Studies; D016019:Survival Analysis; D017211:Treatment Failure