Reduced tumor vessel density and high expression of glucose transporter 1 suggest tumor hypoxia of squamous cell carcinoma of the esophagus surviving after radiotherapy

doi:10.1016/j.surg.2005.01.008

Surgery

Volume 137, Issue 5, May 2005, Pages 536-544

https://doi.org/10.1016/j.surg.2005.01.008 Get rights and content

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.

Section snippets

Patients

From 1985 to 2003, a total of 714 patients underwent esophagectomy caused by thoracic esophageal cancer at the Osaka Medical Center for Cancer and Cardiovascular Diseases; 48 patients had received radiotherapy before the operation. Excluding 4 patients diagnosed as having cT1 or cT2 tumor before treatment, this study enrolled 44 patients with cT3 or cT4 tumor, all of which were squamous cell carcinoma of the esophagus (ESCC), located in the upper (11 patients), middle (21 patients), and lower

Morphologic characteristics of ESCC after radiotherapy

Table II compares the morphologic features of irradiated ESCC with those of untreated ones. ESCC after radiation was apparently different in their morphology, showing shorter tumor length, thinner esophageal wall, more frequent deep ulceration, and less frequent round wall formation. No difference was observed between the neoadjuvant and radical radiation groups. Since the depth of tumor invasion varied among the ESCC after irradiation, their relationship with the morphology was investigated (

Discussion

The purpose of this study was to examine the implications of tumor hypoxia in the spread of ESCC after radiation by comparing surgical specimens of advanced ESCC after radiotherapy with specimens from ESCC without any preoperative treatment. Immunohistochemical study revealed reduction of tumor vessels and increased tumor hypoxia, as shown by GLUT1 expression, in ESCC after radiation. The tumor vessel is a target of radiotherapy and synergy of radiation injury on both the tumor vessel and the

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Original communicationReduced tumor vessel density and high expression of glucose transporter 1 suggest tumor hypoxia of squamous cell carcinoma of the esophagus surviving after radiotherapy

Background

Methods

Results

Conclusions

Section snippets

Patients

Morphologic characteristics of ESCC after radiotherapy

Discussion

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

J Thorac Cardiovasc Surg

Cancer Cell

Surgery

Surgery

Am J Pathol

Am J Surg

INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy

J Clin Oncol

Complications of salvage esophagectomy

Med Sci Monit

Esophageal carcinoma: 2-stage operation for preventing mediastinitis in high risk patients

Chirurg

Importance of additional microvascular anastomosis in esophageal reconstruction after salvage esophagectomy

Plast Reconstr Surg

Evaluation of the histologic effect of chemoradiation therapy for squamous cell carcinomas of the esophagus by assessing morphologic features of surgical specimens

Dis Esophagus

Significance of post-chemoradiation biopsy in predicting residual esophageal carcinoma in the surgical specimen

Dis Esophagus

Tumour hypoxia: impact on biology, prognosis and treatment of solid malignant tumours

Onkologie

Investigating hypoxic tumor physiology through gene expression patterns

Oncogene

Principles and practice of radiation oncology

Original communication
Reduced tumor vessel density and high expression of glucose transporter 1 suggest tumor hypoxia of squamous cell carcinoma of the esophagus surviving after radiotherapy