Abstract
BackgroundHepatocarcinogenesis is a multistep process characterized in patients with chronic liver diseases by a spectrum of hepatic nodules that mark the progression from regenerative nodules to dysplastic lesions followed by hepatocellular carcinoma (HCC). The differential diagnosis between precancerous dysplastic nodules and early HCC still represents a challenge for both radiologists and pathologists. We addressed the potential of Fourier transform-infrared (FTIR) microspectroscopy for grading cirrhotic nodules on frozen tissue sections.MethodsThe study was focused on 39 surgical specimens including normal livers (n = 11), dysplastic nodules (n = 6), early HCC (n = 1), progressed HCC on alcoholic cirrhosis (n = 10) or hepatitis C virus cirrhosis (n = 11). The use of the bright infrared source emitted by the synchrotron radiation allowed investigating the biochemical composition at the cellular level. Chemical mapping on whole tissue sections was further performed using a FTIR microscope equipped with a laboratory-based infrared source. The variance was addressed by principal component analysis.ResultsProfound alterations of the biochemical composition of the pathological liver were demonstrated by FTIR microspectroscopy. Indeed, dramatic changes were observed in lipids, proteins and sugars highlighting the metabolic reprogramming in carcinogenesis. Quantifiable spectral markers were characterized by calculating ratios of areas under specific bands along the infrared spectrum. These markers allowed the discrimination of cirrhotic nodules, dysplastic lesions and HCC. Finally, the spectral markers can be measured using a laboratory FTIR microscope that may be easily implemented at the hospital.ConclusionMetabolic reprogramming in liver carcinogenesis can constitute a signature easily detectable using FTIR microspectroscopy for the diagnosis of precancerous and cancerous lesions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0763-6) contains supplementary material, which is available to authorized users.
Highlights
Hepatocarcinogenesis is a multistep process characterized in patients with chronic liver diseases by a spectrum of hepatic nodules that mark the progression from regenerative nodules to dysplastic lesions followed by hepatocellular carcinoma (HCC)
Hepatocarcinogenesis is a multistep process that is characterized in most cirrhotic livers by the progression from hyperplastic regenerative nodules to low grade dysplastic nodules (LGDN), high grade dysplastic nodules (HGDN) and small HCC which corresponds either to vaguely nodular well differentiated HCC (WDHCC) so called early HCC or to distinctly nodular moderately differentiated hepatocellular carcinomas [3,4,5,6,7,8,9]
We demonstrated that Fourier transforminfrared (FTIR) microspectroscopy exhibits the potentiality to detect the chemical changes occurring in hepatocarcinogenesis and to discriminate benign cirrhotic nodules, premalignant and malignant nodules in cirrhotic liver
Summary
Hepatocarcinogenesis is a multistep process characterized in patients with chronic liver diseases by a spectrum of hepatic nodules that mark the progression from regenerative nodules to dysplastic lesions followed by hepatocellular carcinoma (HCC). The differential diagnosis between high-grade dysplastic nodules (HGDN) and WDHCC still represents a challenge even for experienced pathologists, especially on biopsy specimens as the only discriminative feature is the presence of focal stromal invasion [5]. The morphological criteria which define early HCC such as cell density, thickness of liver cell plates, presence of pseudoglands, loss of reticulin, CD34 expression, small cell dysplasia and stromal invasion [3, 6] are present in high grade dysplastic nodules without clearcut frontier between both lesions. Specific biomarkers of early stages of HCC are still lacking [15]
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