Role of hypoxia-inducible factor-1α, carbonic anhydrase-IX, glucose transporter-1 and vascular endothelial growth factor associated with lymph node metastasis and recurrence in patients with locally advanced cervical cancer

• Published in: Oncology letters Vol. 10; no. 4; pp. 1970 - 1978
• Main Authors: IWASAKI, KEITA, YABUSHITA, HIROMITSU, UENO, TAIKI, WAKATSUKI, AKIHIKO
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01-10-2015; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Angiogenesis; Cancer therapies; carbonic anhydrase-IX; Cervical cancer; Glucose; glucose transporter-1; Glycoproteins; Gynecology; Histology; Hypoxia; hypoxia-inducible factor-1α; Hysterectomy; immunohistochemistry; Immunotherapy; Lymphatic system; Medical prognosis; Metastasis; Obstetrics; Oncology; Patients; Physiological aspects; Radiation therapy; Rodents; Transcription factors; Tumors; Vascular endothelial growth factor; Japan; hypoxia-inducible factor-1α; glucose transporter-1; immunohistochemistry; carbonic anhydrase-IX; cervical cancer; vascular endothelial growth factor
• DOI: 10.3892/ol.2015.3524
• EISSN: 1792-1082
• ISSN: 1792-1074

The aim of the present study was to determine whether the expression of hypoxia-inducible factor-1α (HIF-1α), carbonic anhydrase-IX (CA-IX), glucose transporter-1 (GLUT-1) or vascular endothelial growth factor (VEGF) was associated with the clinicopathological characteristics, lymph node metastasis or progression-free survival of patients with cervical cancer. Tumor tissue samples were obtained from 54 cervical cancer patients who had undergone radical hysterectomy. The expression of HIF-1α, CA-IX, GLUT-1 and VEGF was analyzed by immunohistochemical staining. Of the 54 cases, 28 were positive for HIF-1α, 35 for CA-IX, 40 for GLUT-1 and 23 for VEGF. It was revealed that HIF-1α expression was correlated with tumor stage and histology, CA-IX expression with tumor stage, tumor size, lymph node metastasis and lymph-vascular space involvement, GLUT-1 expression with tumor stage and lymph-vascular space involvement, and VEGF expression with microvessel density. The multivariate regression analysis indicated that CA-IX expression and lymph-vascular space involvement were independent variables associated with lymph node metastasis. Progression-free survival was shorter for patients who were positive for CA-IX or VEGF expression than for those who were negative for CA-IX or VEGF expression. The progression-free survival of patients treated with radiotherapy or chemo-radiotherapy following radical hysterectomy was also shorter for patients with positive CA-IX expression. These findings suggest that CA-IX expression is a possible risk factor for lymph node metastasis and disease recurrence in locally advanced cervical cancer patients.