Oncotarget

Research Papers:

A close relationship between HIF-1α expression and bone metastases in advanced NSCLC, a retrospective analysis

Aldo Pezzuto, Giuseppe Perrone, Nicoletta Orlando, Fabrizio Citarella _, Massimo Ciccozzi, Simone Scarlata and Giuseppe Tonini

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Oncotarget. 2019; 10:7071-7079. https://doi.org/10.18632/oncotarget.27378

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Abstract

Aldo Pezzuto1, Giuseppe Perrone2, Nicoletta Orlando2, Fabrizio Citarella3, Massimo Ciccozzi4, Simone Scarlata5 and Giuseppe Tonini3

1 Cardiovascular-Respiratory Science Department, Sant’ Andrea Hospital-Sapienza University, Rome, Italy

2 Department of Pathology, Policlinico Campus Bio-Medico di Roma, Rome, Italy

3 Oncology Department, Policlinico Campus Bio-Medico di Roma, Rome, Italy

4 Department of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico, Rome, Italy

5 Department of Internal Medicine, University Campus Bio-Medico, Rome, Italy

Correspondence to:

Fabrizio Citarella,email: f.citarella@unicampus.it

Keywords: HIF-1α expression; lung cancer; bone metastases; time to progression

Received: August 06, 2019     Accepted: November 23, 2019     Published: December 17, 2019

ABSTRACT

Background: Hypoxia-inducible factor (HIF-1) is a transcription factor produced in hypoxia condition, it is closely associated with tumor angiogenesis and metastasis.

Aim: To investigate the expression of HIF-1α in relation with the presence or absence of bone metastasis. Methods A retrospective analysis was carried out on samples deriving from bronchial biopsy and CT-guided trans-thoracic needle biopsy. Detection of HIF-1 expression was performed on tissue sample by a monoclonal murine antibody, comparing patients with or without bone metastases (BM+).

Findings: In the total population the main histotype was adenocarcinoma (71.5%), COPD the prevalent comorbidity (73.6%), the mean pack-year was 36.4. Ninety-five histology samples were considered for analysis and comparison. Subdividing the population according to the presence or not of bone metastases, significant differences were found in pack-years (p = 0.02), time to progression (TTP) (p = 0.001) and COPD comorbidity (p = 0.04). The survival comparison between the two subgroups obtained by Kaplan–Meier method showed a longer TTP in patients with visceral metastases with a HR of 1.3 though the comparison by this method was not significant (p = 0.1). A higher intensity and percentage of expression of HIF-1α was recorded in the group with bone metastases (p = 0.02). The main variable affecting HIF expression in a multivariate analysis was the presence of bone metastases (p = 0.01).

Interpretation: Patients affected by NSCLC IV stage with bone metastasis have lower survival. There is a very close link between bone metastasis and HIF-1α expression level. The latter could be considered a predictive factor of bone spread and poor prognosis.


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