title: 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.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Iwasaki
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Yabushita
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Wakatsuki
keywords: carbonic anhydrase-IX; cervical cancer; glucose transporter-1; hypoxia-inducible factor-1α; immunohistochemistry; vascular endothelial growth factor