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Alterations of glycosaminoglycans in human liver and kidney tumors
1I. Institute of Pathology and Experimental Cancer Research, Semmelweis Medical University, Budapest, Hungary.
Abstract:
Glycosaminoglycans were investigated in surgically removed human liver and kidney tumours by applying biochemical methods. Four liver adenoma, 6 focal nodular hyperplasia and 9 primary hepatocellular carcinoma samples were compared with normal liver from autopsy cases and also with liver tissue adjacent to PHC. The studies on kidney included 14 renal cell carcinoma and 4 wilms' tumour samples. Three findings emerged from the quantitative and qualitative characterization of the tumours with epithelial origin. 1) The rise in the amount of total GAG was not limited to the malignant lesion. Similar increase was observed in benign liver tumours and also in the tissue adjacent to liver or kidney malignant tumours. 2) The dominant type of the GAG subclasses varies with the histology of the tumours. In benign liver tumours dermatan sulfate, in PHC and renal cell carcinoma chondroitin sulfate, but in Wilms' tumour hyaluronate was the prominent GAG subclass. 3) In all tumour-affected tissues dermatan and chondroitin sulfates had lower degree of sulfation. However, in the histologically different tumours various disaccharides showed reduced level of sulfation. The GAG alteration in renal cell carcinoma was compared with the prognostic factors of each individual case. This analysis showed a good correlation between HS/CS ratio and the prognostic factors of the kidney tumour cases.
Insights
Glycosaminoglycans (GAGs) increase in both benign and malignant liver and kidney tumors, with specific GAG types varying by tumor histology. Altered sulfation patterns in GAGs correlate with tumor prognosis.
Area of Science:
- Biochemistry
- Oncology
- Histopathology
Background:
- Glycosaminoglycans (GAGs) are crucial components of the extracellular matrix.
- Alterations in GAG composition and structure are associated with various pathological conditions, including cancer.
Purpose of the Study:
- To investigate the quantitative and qualitative changes in GAGs in human liver and kidney tumors.
- To compare GAG profiles in benign and malignant tumors with adjacent non-tumorous tissues and normal controls.
- To explore the relationship between GAG alterations and prognostic factors in renal cell carcinoma.
Main Methods:
- Biochemical analysis of surgically removed human liver and kidney tumor samples.
- Quantitative and qualitative characterization of glycosaminoglycans.
- Histological classification of tumors (liver adenoma, focal nodular hyperplasia, primary hepatocellular carcinoma, renal cell carcinoma, Wilms' tumor).
Main Results:
- Increased total GAG amounts were observed in benign liver tumors and adjacent tissues, not just malignant lesions.
- Dominant GAG subclasses varied: dermatan sulfate in benign liver tumors, chondroitin sulfate in primary hepatocellular carcinoma and renal cell carcinoma, and hyaluronate in Wilms' tumor.
- Tumor-associated GAGs (dermatan and chondroitin sulfates) exhibited reduced sulfation, with varying disaccharide sulfation levels across different tumor types.
- A significant correlation was found between the heparan sulfate/chondroitin sulfate (HS/CS) ratio and prognostic factors in renal cell carcinoma cases.
Conclusions:
- GAG alterations, including increased amounts and modified sulfation, are characteristic of both benign and malignant liver and kidney tumors.
- Specific GAG subclass dominance is linked to tumor histology.
- GAG profiles, particularly the HS/CS ratio, may serve as potential biomarkers for tumor prognosis, especially in renal cell carcinoma.