Clinicopathological and prognostic significance of HIF-1¦Á and HIF-2¦Á expression in small cell lung cancer

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• 作者：Yajing Luan ^{yajingluan123@126.com} ; Cuicui Gao ; Yajing Miao ^{miao_yajing@163.com} ; Yanlei Li ^{dylylnj@163.com} ; Zhengyan Wang ^{sdwangzhengyan@yahoo.com.cn} ; Xiaofei Qiu ; ^{qiouxf@tijmu.edu.cn}
• 关键词：HIF-1¦Á ; HIF-2¦Á ; Small cell lung cancer ; Clinicopathological features ; Prognosis
• 刊名：Pathology - Research and Practice
• 出版年：2013
• 出版时间：March, 2013
• 年：2013
• 卷：209
• 期：3
• 页码：184-189
• 全文大小：956 K

文摘

Previous work from our laboratory has demonstrated that urokinase plasminogen activator receptor (uPAR) may be a potential stem-like cell marker in SCLC. Hypoxia inducible factor (HIF) has been shown to transcriptionally regulate uPAR expression. Therefore, the aim of this study was to evaluate the relationship between HIF-1¦Á/HIF-2¦Á and uPAR expression, and to investigate the role of HIF-1¦Á/HIF-2¦Á in the clinical pathology and prognosis of patients with SCLC. Immunohistochemical analysis showed that HIF-1¦Á/HIF-2¦Á staining was mainly present in the nuclei of cancer cells. HIF-1¦Á-positive cells were diffusely distributed in the nests of the tumor, while HIF-2¦Á-positive cells were frequently distributed around necrotic regions. HIF-1¦Á and HIF-2¦Á were expressed in 22/45 (48.9 % ) and in 11/45 (24.4 % ) of SCLC patients, respectively; HIF-1¦Á did not correlate with any of the clinicopathological parameters as evaluated in our study. In contrast, a significant association of HIF-2¦Á with uPAR expression, tumor growth and distant metastasis (p = 0.001, 0.010 and 0.008, respectively) was noted; Kaplan-Meier survival analysis demonstrated that HIF-1¦Á and HIF-2¦Á expressions were related to shortened overall survival (p = 0.027 and 0.001, respectively). However, in multivariate analysis, only HIF-2¦Á expression and distant metastasis were the independent prognostic indicators of SCLC (p = 0.004 and 0.018, respectively). Our results suggest that HIF-2¦Á may represent a more aggressive phenotype in SCLC. HIF-2¦Á, in addition to HIF-1¦Á, needs to be considered when developing drugs that target HIF pathway.