Relationships between radiosensitivity and microvascular density in esophageal carcinoma: significance of hypoxic fraction.
OBJECTIVE
The prognosis and the radiosensitivity of macroscopically infiltrative type of esophageal carcinoma are worse than those of the localized type of esophageal carcinoma treated with irradiation. The aim of this study was to investigate the cause of differences in radiosensitivity and prognosis of esophageal carcinoma according to macroscopic type from the viewpoint of tumor angiogenesis.


METHODS
A total of 40 surgically resected esophageal carcinoma tissues with good material remaining were selected at random from macroscopically localized type (n = 20) and infiltrative type (n = 20) of esophageal carcinoma. The highest intratumoral microvascular density (h-MVD), average intratumoral microvascular density (a-MVD), Ki67 labeling index, and expression of vascular endothelial growth factor (VEGF) in each section were estimated.


RESULTS
h-MVD was significantly (p = 0.0006) greater in the infiltrative type than in the localized type, whereas a-MVD (p = 0.0014) and Ki67 labeling index (p = 0.022) were significantly lower in the infiltrative type than in the localized type. The expression level of VEGF was significantly (p < 0.0001) higher in the infiltrative type.


CONCLUSIONS
The generally underdeveloped vascular densities with low proliferation activities (suggesting increase of hypoxic fraction) seemed to be one of the reasons for unfavorable radiosensitivities of infiltrative type of esophageal carcinoma. The infiltrative type of esophageal carcinoma shows a high level of VEGF expression and high activity of tumor angiogenesis. The locally enhanced neovascularization, which occurs frequently in hematogenous metastasis seemed to be one of the reasons for the unfavorable prognosis of the infiltrative type of esophageal carcinoma.
Nomiya
Takuma
T
Department of Radiation Oncology, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai 980-8574, Japan. nomiya@rad.med.tohoku.ac.jp
Nemoto
Kenji
K
Miyachi
Hideo
H
Fujimoto
Keisuke
K
Takeda
Ken
K
Ogawa
Yoshihiro
Y
Takai
Yoshihiro
Y
Yamada
Shogo
S
D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000473:pathology / Q000532:radiotherapy*; D015687:Cell Hypoxia; D004938:Esophageal Neoplasms / Q000098:blood supply* / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D011379:Prognosis; D011836:Radiation Tolerance; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D018952:Antigens, CD34; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D042461:Vascular Endothelial Growth Factor A