Positron emission tomography-computed tomography and 4-hydroxynonenal-histidine immunohistochemistry reveal differential onset of lipid peroxidation in primary lung cancer and in pulmonary metastasis of remote malignancies

Nevenka Piskač Živković,Mladen Petrovečki,Čedna Tomasović Lončarić,Igor Nikolić,Georg Waeg,Morana Jaganjac,Kamelija Žarković,Neven Žarković

doi:10.1016/j.redox.2017.01.005

Abstract

The Aim of the study was to reveal if PET-CT analysis of primary and of secondary lung cancer could be related to the onset of lipid peroxidation in cancer and in surrounding non-malignant lung tissue. MethodsNineteen patients with primary lung cancer and seventeen patients with pulmonary metastasis were involved in the study. Their lungs were analyzed by PET-CT scanning before radical surgical removal of the cancer. Specific immunohistochemistry for the major bioactive marker of lipid peroxidation, 4-hydroxynonenal (HNE), was done for the malignant and surrounding non-malignant lung tissue using genuine monoclonal antibody specific for the HNE-histidine adducts. ResultsBoth the intensity of the PET-CT analysis and the HNE-immunohistochemistry were in correlation with the size of the tumors analyzed, while primary lung carcinomas were larger than the metastatic tumors. The intensity of the HNE-immunohistochemistry in the surrounding lung tissue was more pronounced in the metastatic than in the primary tumors, but it was negatively correlated with the cancer volume determined by PET-CT. The appearance of HNE was more pronounced in non-malignant surrounding tissue than in cancer or stromal cells, both in case of primary and metastatic tumors. ConclusionsBoth PET-CT and HNE-immunohistochemistry reflect the size of the malignant tissue. However, lipid peroxidation of non-malignant lung tissue in the vicinity of cancer is more pronounced in metastatic than in primary malignancies and might represent the mechanism of defense against cancer, as was recently revealed also in case of human liver cancer.

Highlights

The basic feature of a tumor cell is the metabolic switch from oxidative phosphorylation to anaerobic glycolysis even under circumstances of normal oxygen saturation, a phenomenon known as the Warburg effect [1]
No statistically significant difference was established between HNEintensity in the cytoplasm of tumor cells that were exposed to neoadjuvant chemotherapy when compared to those who were not treated by chemotherapy
The mean tumor volume of the secondary, metastatic tumors was significantly smaller than was the mean primary lung tumor volume prior to resection, probably due to the fact that the patients with metastatic cancer had been actively followed by imaging methods to monitor the onset of metastasis of their primary tumor

Summary

Introduction

The basic feature of a tumor cell is the metabolic switch from oxidative phosphorylation to anaerobic glycolysis even under circumstances of normal oxygen saturation, a phenomenon known as the Warburg effect [1]. Lactate dehydrogenase (LDHA) catalyzes the conversion of pyruvate to lactate, and is considered the key enzyme that regulates anaerobic metabolism, including the increased expression of the Glut-1 to Glut-4 transport proteins [2,3]. The mentioned tumor cell feature is used in the diagnostic method of Positron Emission Tomography and Computed Tomography (PET-CT) scanning. In the majority of clinical studies, a SUV of > 2.5 is considered the cut-off value indicating a malignant etiology of the pulmonary nodule [7,8,9,10,11,12] (Fig. 1)

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Results

Conclusion