Reduced tumor vessel density and high expression of glucose transporter 1 suggest tumor hypoxia of squamous cell carcinoma of the esophagus surviving after radiotherapy.
BACKGROUND
Squamous cell carcinoma of the esophagus (ESCC) is radiosensitive; however, surgeons frequently encounter ESCC that survives radiotherapy to grow more rapidly and invasively. This alteration of tumor behavior may result from tumor hypoxia induced by radiotherapy.


METHODS
Forty-four patients with advanced (T3 and T4) ESCC, who underwent radiotherapy before operation, either with 40 Gy for preoperative treatment or 60 Gy or more for radical treatment, and 44 patients without preoperative therapy were subjected to retrospective immunohistochemical study. CD34 for tumor vessels, glucose transporter 1 (GLUT1) which was induced by hypoxia, MIB-1 for proliferating activity, and p53 were stained for surgical samples from ESCC patients. Tumor tissue at the invading front was the focus of evaluation. Macroscopic morphologic differences of ESCC were also evaluated.


RESULTS
Loss of esophageal wall thickness and deep ulceration were morphologic characteristics of ESCC after radiotherapy. Tumor vessel density was reduced and GLUT1 expression was greater in the ESCC after radiotherapy than in those without treatment. Tumor vessel density was similar for both preoperative and radical radiotherapy samples, while GLUT1 expression tended to be greater in the latter than in the former. The expression of MIB-1 and p53 did not show any significant difference between ESCC with or without radiotherapy.


CONCLUSIONS
Reduced vessel density and increased GLUT1 expression suggested tumor hypoxia for ESCC occurred after radiotherapy. Tumor hypoxia would induce ulcerative and invasive growth, which is a great obstacle to clinical treatment of residual or relapse ESCC after radiotherapy.
Doki
Yuichiro
Y
Department of Digestive Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka City, Japan. ydoki@surg2.med.osaka-u.ac.jp
Takachi
Ko
K
Ishikawa
Osamu
O
Sasaki
Yo
Y
Miyashiro
Isao
I
Ohigashi
Hiroaki
H
Yano
Masahiko
M
Ishihara
Ryu
R
Tsukamoto
Yoshitane
Y
Nishiyama
Kinji
K
Ishiguro
Shingo
S
Imaoka
Shingi
S
D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000378:metabolism* / Q000532:radiotherapy; D016022:Case-Control Studies; D015687:Cell Hypoxia / Q000528:radiation effects; D004938:Esophageal Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000532:radiotherapy; D005260:Female; D051272:Glucose Transporter Type 1; D006801:Humans; D008297:Male; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011878:Radiotherapy / Q000009:adverse effects
D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human