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

Kim JI, Choi KU, Lee IS, Choi YJ, Kim WT, Shin DH, Kim K, Lee JH, Kim JY, Sol MY - Oncol Lett (2015)

Bottom Line: Overexpression of HIF-1α and CA9 was associated with a shorter OS and a shorter PFS.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier survival curves showing disease-free survival and overall survival for soft tissue sarcoma patients with HIF-1α and CA9 expression. HIF-1α, hypoxia-inducible factor 1α; CA9, carbonic anhydrase 9; FU, follow-up; DFSP, disease-fee survival period.
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f3-ol-09-04-1699: Kaplan-Meier survival curves showing disease-free survival and overall survival for soft tissue sarcoma patients with HIF-1α and CA9 expression. HIF-1α, hypoxia-inducible factor 1α; CA9, carbonic anhydrase 9; FU, follow-up; DFSP, disease-fee survival period.

Mentions: Of the 30 patients exhibiting HIF-1α expression, 22 (73.3%) showed disease progression and 23 (76.7%) died from the disease, compared with only nine (36%) and four (16%), respectively, of the 25 patients who did not display HIF-1α expression. These differences were statistically significant (P=0.007 and 0.042, respectively). However, the expression of GLUT1 and VEGF was not associated with disease progression and survival (Table III). To investigate the prognostic impact of these markers in STS, Kaplan-Meier survival analyses were conducted and the differences in survival between the groups were examined. The Kaplan-Meier survival curves (Fig. 3) indicated that HIF-1α and CA9 expression had a significant impact on disease free survival (P=0.001 and 0.006) and OS (P=0.001 and 0.003). Multivariate analyses revealed that advanced AJCC stage (P=0.011) and HIF-1α expression (P=0.006) were independent prognostic markers for OS compared with early AJCC stage and no HIF-1α overexpression (Table IV). In the group receiving chemotherapy (n=27), HIF-1α expression was independently associated with shorter survival, and was an independent prognostic factor on multivariate analysis (P=0.010) (Table V).


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

Kim JI, Choi KU, Lee IS, Choi YJ, Kim WT, Shin DH, Kim K, Lee JH, Kim JY, Sol MY - Oncol Lett (2015)

Kaplan-Meier survival curves showing disease-free survival and overall survival for soft tissue sarcoma patients with HIF-1α and CA9 expression. HIF-1α, hypoxia-inducible factor 1α; CA9, carbonic anhydrase 9; FU, follow-up; DFSP, disease-fee survival period.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4356356&req=5

f3-ol-09-04-1699: Kaplan-Meier survival curves showing disease-free survival and overall survival for soft tissue sarcoma patients with HIF-1α and CA9 expression. HIF-1α, hypoxia-inducible factor 1α; CA9, carbonic anhydrase 9; FU, follow-up; DFSP, disease-fee survival period.
Mentions: Of the 30 patients exhibiting HIF-1α expression, 22 (73.3%) showed disease progression and 23 (76.7%) died from the disease, compared with only nine (36%) and four (16%), respectively, of the 25 patients who did not display HIF-1α expression. These differences were statistically significant (P=0.007 and 0.042, respectively). However, the expression of GLUT1 and VEGF was not associated with disease progression and survival (Table III). To investigate the prognostic impact of these markers in STS, Kaplan-Meier survival analyses were conducted and the differences in survival between the groups were examined. The Kaplan-Meier survival curves (Fig. 3) indicated that HIF-1α and CA9 expression had a significant impact on disease free survival (P=0.001 and 0.006) and OS (P=0.001 and 0.003). Multivariate analyses revealed that advanced AJCC stage (P=0.011) and HIF-1α expression (P=0.006) were independent prognostic markers for OS compared with early AJCC stage and no HIF-1α overexpression (Table IV). In the group receiving chemotherapy (n=27), HIF-1α expression was independently associated with shorter survival, and was an independent prognostic factor on multivariate analysis (P=0.010) (Table V).

Bottom Line: Overexpression of HIF-1α and CA9 was associated with a shorter OS and a shorter PFS.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

No MeSH data available.


Related in: MedlinePlus