Expression of hypoxia-inducible factor 1α, hypoxia-inducible factor 2α, and von Hippel–Lindau protein in epithelial ovarian neoplasms and allelic loss of von Hippel-Lindau gene: nuclear expression of hypoxia-inducible factor 1α is an independent prognostic factor in ovarian carcinoma

Osada, Ryosuke; Horiuchi, Akiko; Kikuchi, Norihiko; Yoshida, Junko; Hayashi, Akiko; M, Ota; Katsuyama, Yoshihiko; Mellilo, Giovanni; Konishi, Ikuo

doi:10.1016/j.humpath.2007.02.010

Cited by 113 publications

(99 citation statements)

References 33 publications

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“…The signature contains several genes previously reported as OCCC markers, such as HNF-1b (Tsuchiya et al, 2003), secreted phosphoprotein 1 (Kato and Motoyama, 2008) and HIF-1a (Lee et al, 2007;Osada et al, 2007), again supporting that this signature is based on the selective extraction of a subset of biologically important and unique genes specific to OCCC. As shown in Tables 2a and b and Supplementary Tables 4a and b, genes categorized within the following GO term are significantly segregated in the OCCC signature: SUPEROXIDE_METABOLIC_PROCESS and RE-SPONSE_TO_OXIDATIVE_STRESS, which indicates oxidative stress; CYTOKINE_BIOSYNTHETIC_ PROCESS, which indicates inflammation; and POSITIVE_ REGULATION_OF_MAP_KINASE_ACTIVITY, which indicates an activated mitogen-activated protein kinase pathway, known as a stress signaling pathway.…”

Section: Resultssupporting

confidence: 61%

Identification of an ovarian clear cell carcinoma gene signature that reflects inherent disease biology and the carcinogenic processes

et al. 2010

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Section: Resultssupporting

confidence: 61%

Identification of an ovarian clear cell carcinoma gene signature that reflects inherent disease biology and the carcinogenic processes

et al. 2010

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“…Under anoxic conditions, HIF-1α is activated and regulates transcription of various downstream target genes and acts to maintain anaerobic metabolism of tumor cells. In addition, it also promotes neovascularization, thus enhancing tumor survival, growth, and metastasis (Osada et al, 2007). In this study, expression of HIF-1α was noted in 64.18% (43/67) of cervical squamous cell carcinoma cases, which differed significantly from that of normal cervical tissues (P < 0.05).…”

Section: Discussionmentioning

confidence: 50%

Vasculogenic mimicry and hypoxia-inducible factor-1α expression in cervical squamous cell carcinoma

Zhou¹,

Huang²,

Gong³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. In this study, the existence of vasculogenic mimicry (VM) in cervical squamous cell carcinoma was investigated. To this end, the relationship between hypoxia-inducible factor 1α (HIF-1α) and the development, infiltration, and metastasis of cervical squamous cell carcinoma was studied. Between January 2010 and December 2010, 67 human cervical squamous carcinoma tissue samples were collected and stained by CD34/periodic acid-Schiff double staining to detect the existence of VM. HIF-1α expression was analyzed by immunohistochemistry. The relationship between VM and HIF-1α was also analyzed. Normal cervical tissues (20 cases) from patients who had uterine surgeries in the same period were collected as controls. In the cervical squamous carcinoma tissues, positive rates of VM and HIF-1α were 38.81% (26/67) and 64.18% (43/67), respectively. This was significantly higher than those in the normal cervical tissues [0 (0/20); P < 0.05]. VM rates in cervical squamous carcinoma tissues from patients with different pathological grades, Federation of Gynecology and Obstetrics (FIGO) stages, and lymph node metastasis states were also significantly different (P < 0.05). In addition, significant differences in HIF-1α positivity rates were observed among patients with varying tumor sizes and lymph node metastasis states (P < 0.05). Positive correlation was found between VM and HIF-1α (r = 0.339, P < 0.05). To summarize, we found VM in cervical squamous carcinoma; high expression of HIF-1α may promote VM formation, as well as cervical squamous cell infiltration and metastasis.

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“…Lee et al also studied HIF-1α expression in ovarian cancers and they found that, in clear cell tumors HIF-1α wa expressed more than in endometrioid and serous cell cancers (20). On the other hand, Osada et al found that there was no difference in HIF-1α expression of various histological types of ovarian cancers (21).…”

Section: Discussionmentioning

confidence: 99%

The investigation of tumoral angiogenesis with HIF-1 alpha and microvessel density in women with endometrium cancer

Aybatli¹,

Sayın²,

Kaplan³

et al. 2012

J Turkish German Gynecol Assoc

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Objective: Hypoxia inducible factor 1 alpha (HIF-1α) is a nuclear protein upregulated in response to reduced cellular oxygen concentration which therefore acts as a marker for hypoxia. The aim of this study was to determine tumoral angiogenesis with immunohistochemical markers in endometrium cancer and its relation with stage, grade, survival rates and other prognostic factors. Material and Methods:Using the database in our Gynecologic Oncology clinic, we selected 94 patients who were diagnosed with endometrial cancer and underwent primary surgery at our institution between 2001 and 2010. Tissue microarrays believed to demonstrate the optimum part of the tumor were reprepared from the paraffin blocks. Angiogenesis and microvessel density (MVD) were investigated with the aid of HIF-1α and CD34 antibodies.Results: High expression of HIF-1α was significantly more frequent in advanced grade endometrial cancers (p=0.044). HIF-1α expression was highly correlated with CD34 expression in the tumor cells (p<0.001). However lack of relation among stage, overall survival rates and histological types were analyzed with HIF-1α. When we compared HIF-1α positive and negative cases with cervical, adnexial, lymphovascular and myometrial invasion, there was no difference between these groups. MVD was evaluated with CD34 and it was remarkable and significantly different on advanced grade tumors (r=0.268; p=0.009). A similar significant difference was observed between the high expression of CD34 and type II endometrial cancer histology (p<0.001). However, there was no relationship between the MVD and stage or survival rates. Conclusion:High expression of HIF-1α is associated with tumoral angiogenesis in endometrial adenocarcinomas. Further studies targeting HIF-1α for disrupting mechanisms essential for tumor growth in endometrium cancer will be significant investigations in the future. (J Turkish-German Gynecol Assoc 2012; 13: 37-44) Key words: Endometrium cancer, HIF-1α, hypoxia, angiogenesis Received: 21 April, 2011 Accepted: 3 December, 2011 Amaç: Hipoksi ile indüklenen faktör-1α (HIF-1 α) bir nükleer proteindir ve azalan hücre içi oksijen konsantrasyonuna cevap olarak regüle edilir. Bu nedenle bir hipoksi belirteci gibi görev yapar. Bu çalışmanın amacı endometrium kanserli olgularda tümör anjiogenezini immunohistokimyasal belirteçler ile incelemek ve evre, derece ve sağkalım gibi prognostik faktörlerle olan bağlantısını aydınlatmaya çalışmaktır.

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Expression of hypoxia-inducible factor 1α, hypoxia-inducible factor 2α, and von Hippel–Lindau protein in epithelial ovarian neoplasms and allelic loss of von Hippel-Lindau gene: nuclear expression of hypoxia-inducible factor 1α is an independent prognostic factor in ovarian carcinoma

Cited by 113 publications

References 33 publications

Identification of an ovarian clear cell carcinoma gene signature that reflects inherent disease biology and the carcinogenic processes

Identification of an ovarian clear cell carcinoma gene signature that reflects inherent disease biology and the carcinogenic processes

Vasculogenic mimicry and hypoxia-inducible factor-1α expression in cervical squamous cell carcinoma

The investigation of tumoral angiogenesis with HIF-1 alpha and microvessel density in women with endometrium cancer

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