Expression of hypoxic markers and their prognostic significance in soft tissue sarcoma

Kim,Jeung  Il; Choi,Kyung  Un; Lee,In  Sook; Choi,Young  Jin; Kim,Won  Tack; Shin,Dong  Hoon; Kim,Kyungbin; Lee,Jeong  Hee; Kim,Jee  Yeon; Sol,Mee  Young

doi:10.3892/ol.2015.2914

Expression of hypoxic markers and their prognostic significance in soft tissue sarcoma

Authors:
- Jeung Il Kim
- Kyung Un Choi
- In Sook Lee
- Young Jin Choi
- Won Tack Kim
- Dong Hoon Shin
- Kyungbin Kim
- Jeong Hee Lee
- Jee Yeon Kim
- Mee Young Sol
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Affiliations: Department of Orthopedics, Pusan National University Hospital, Busan 602‑739, Republic of Korea, Medical Research Institute, Pusan National University Hospital, Busan 602‑739, Republic of Korea, Department of Radiology, Pusan National University Hospital, Busan 602‑739, Republic of Korea, Department of Internal Medicine, Pusan National University Hospital, Busan 602‑739, Republic of Korea, Department of Therapeutic Radiology and Oncology, Pusan National University Hospital, Busan 602‑739, Republic of Korea, Department of Pathology, Pusan National University Yangsan Hospital, Pusan National University, School of Medicine, Yangsan, Gyeongsangnam‑do 626‑770, Republic of Korea
Published online on: January 28, 2015 https://doi.org/10.3892/ol.2015.2914
Pages: 1699-1706

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Abstract

Tumor hypoxia is significant in promoting tumor progression and resistance to therapy, and hypoxia‑inducible factor 1α (HIF‑1α) is essential in the adaptive response of cells to hypoxia. The aim of the present study was to investigate the expression of hypoxic markers and evaluate their prognostic significance in soft tissue sarcoma (STS). A retrospective analysis of 55 patients with STS from Pusan National University Hospital (Busan, Korea) between 1998 and 2007 was conducted, using immunohistochemistry to analyze the expression of HIF‑1α, carbonic anhydrase 9 (CA9), glucose transporter‑1 (GLUT1) and vascular endothelial growth factor (VEGF). The association between the overexpression of these markers and clinicopathological characteristics, including the overall survival (OS) and progression‑free survival (PFS) in cases of STS, were investigated. Overexpression of HIF‑1α, CA9, GLUT1 and VEGF was shown in 54.5, 32.7, 52.7 and 25.5% of tumors, respectively, and all exhibited a significant association with high French Federation of Cancer Centers (FNCLCC) grade and high American Joint Committee on Cancer (AJCC) stage. Overexpression of HIF‑1α and CA9 was associated with a shorter OS and a shorter PFS. On multivariate analysis, AJCC stage and HIF‑1α overexpression had independent prognostic significance. In the group receiving chemotherapy (n=27), HIF‑1α overexpression was independently associated with a decreased OS. These results indicate that overexpression of HIF‑1α and CA9 is associated with poor prognosis, and that HIF‑1α overexpression is an independent unfavorable prognostic factor in STS.

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