Expression of hypoxia-inducible factor-1 alpha and its prognostic significance in small-sized adenocarcinomas of the lung

Enatsu, Sotarou; Iwasaki, Atsushi; Shirakusa, Takayuki; Hamasaki, Makoto; Nabeshima, Kazuki; Iwasaki, Hiroshi; Kuroki, Motomu; Kuroki, Masahide

doi:10.1016/j.ejcts.2006.03.027

Cited by 36 publications

(34 citation statements)

References 22 publications

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“…57,58 However, a large proportion of human tumors exhibit VEGF-A expression in the absence of HIF-1␣. 39 Although the VEGF-A promoter contains a HIF-1␣ binding site, 58 our study demonstrated negligible HIF-1␣ expression in lung cancer cells cultivated under ordinary conditions, and luciferase reporter assays revealed no significant association between the HIF-1␣ binding site and VEGF-A promoter activity.…”

Section: Discussionmentioning

confidence: 99%

Early Growth Response-1 Induces and Enhances Vascular Endothelial Growth Factor-A Expression in Lung Cancer Cells

Shimoyamada

Yazawa

Sato

et al. 2010

The American Journal of Pathology

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Section: Discussionmentioning

confidence: 99%

Early Growth Response-1 Induces and Enhances Vascular Endothelial Growth Factor-A Expression in Lung Cancer Cells

Shimoyamada

Yazawa

Sato

et al. 2010

The American Journal of Pathology

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“…Low VEGF levels were reported in adenocarcinoma in situ, that is, formerly bronchioloalveolar carcinoma, compared with "conventional adenocarcinoma" (Saad et al 2004). Enatsu et al (2006) observed an association between hypoxia-inducible factor-1α (HIF-1α) and VEGF-A expression in pulmonary adenocarcinomas, and little or no reactivity of HIF-1α was observed in the bronchioloalveolar components, in contrast to the solid components of adenocarcinomas with mixed subtypes. Therefore, the absence of lymphangiogenesis in the areas of lepidic growth might reflect the absence of VEGF secretion by tumor cells, in contrast to the VEGF-C secretion in invasive adenocarcinomas reported by Saintigny et al (2007).…”

Section: Discussionmentioning

confidence: 99%

Morphometry Analysis of Lymphatics in Pulmonary Adenocarcinomas With a Lepidic Growth Pattern

Sannier

Kambouchner

Danel

et al. 2013

J Histochem Cytochem.

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Lymph vessels play an important role in tumor progression. Pulmonary adenocarcinomas, accounting for half of non-small-cell lung carcinomas, compose a spectrum of histological types, exclusively or without a lepidic growth pattern (LGP) along preserved interalveolar septa. In that context, this study was designed to investigate the lymphatic vascular pattern associated with LGP and the concomitant invasive component of pulmonary adenocarcinomas. Using the D2-40 monoclonal antibody as a marker of lymphatic endothelial cells, the lymphatic vessel density (LVD) and vessel-area fraction (LVAF) were morphometrically analyzed in four adenocarcinomas in situ (AIS) and the LGP of eight invasive adenocarcinomas (LPIA), and compared with their invasive pattern (IPIA). LVD in AIS (2.1 ± 0.7 mm−2) and LPIA (2.4 ± 1 mm−2) were significantly lower than that in IPIA (14.9 ± 13.6 mm−2) ( p=0.001). Moreover, the lymphatic vascular pattern in LGP was similar to that of normal lung, with isolated small lymphatic vessels within the interalveolar septa. Our results showing the scarcity of lymphatics in LGP suggest an absence of septal lymphangiogenesis associated with the LGP pattern in lung adenocarcinomas, which could explain, at least partially, the better prognosis observed in tumors with exclusive or predominant lepidic spread compared with other subtypes.

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“…Upregulation of angiogenic pathways by HIF-1alpha has been seen in NSCLC and it is reported as a common event associated with poor prognosis [28,[39][40][41] .…”

Section: Hif-1alpha and Angiogenesismentioning

confidence: 99%

“…HIF-1alpha was reported to be localized both in the nucleus and the cytoplasm of tumor cells. Some authors consider only nuclear staining as positive [31,34] while others take into account cytoplasmic reactivity as well [28,30,39] . The presence and the biological significance of cytoplasmic HIF-1alpha staining in tissue samples are controversial.…”

Section: Hif-1alpha Evaluation In Tissue Specimensmentioning

confidence: 99%

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HIF-1alpha in lung carcinoma: Histopathological evidence of hypoxia targets in patient biopsies

Ιωάννου

Simos²,

Koukoulis³

2013

JST

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Background: Hypoxia inducible factor 1alpha (HIF-1alpha) plays a major role in the response of tumors to hypoxia, and contributes to tumor aggressiveness, invasiveness and resistance to radiotherapy and chemotherapy. Targeting HIF-1alpha is an attractive strategy, with the potential for disrupting multiple pathways crucial for tumor growth. Thus, the evaluation of HIF-1alpha in patient biopsies could be useful in personalized cancer treatment. Methodology:The current literature on HIF-1alpha immunohistochemical expression is reviewed along with the relation to clinical outcome and prognosis. In addition, the significant correlation of HIF-1alpha to vascular endothelial growth factor (VEGF) expression is reported, as well as the possible role of HIF-1alpha in predicting the therapeutic response to anti-EGFR therapies. Conclusion:Herein, an overview of the HIF-1alpha expression in lung carcinoma is presented. Since there is no consensus regarding the assessment of HIF-1alpha in tissue specimens, heterogeneous results have been reported especially regarding prognosis. In this context, methods to optimize the evaluation of HIF-1alpha in biopsies are needed in order to clarify the role of HIF-1alpha as a prognostic or predictive biomarker in lung carcinoma.

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Expression of hypoxia-inducible factor-1 alpha and its prognostic significance in small-sized adenocarcinomas of the lung

Abstract: Immunohistochemical staining of HIF-1 alpha, along with examination of metastatic potential via vascular pathways, may be valid defining a subpopulation of patients with small-sized adenocarcinoma of the lung whose tumors have aggressive angiogenesis potential.

Cited by 36 publications

References 22 publications

Early Growth Response-1 Induces and Enhances Vascular Endothelial Growth Factor-A Expression in Lung Cancer Cells

Early Growth Response-1 Induces and Enhances Vascular Endothelial Growth Factor-A Expression in Lung Cancer Cells

Morphometry Analysis of Lymphatics in Pulmonary Adenocarcinomas With a Lepidic Growth Pattern

HIF-1alpha in lung carcinoma: Histopathological evidence of hypoxia targets in patient biopsies

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