Markers of High Risk and Poor Prognosis in Colorectal GISTs
Markers of High Risk and Poor Prognosis in Colorectal GISTs
Aims Colorectal gastrointestinal stromal tumours (GISTs) are considered to be tumours with a relatively poor prognosis. Few reports have been performed to investigate the mechanisms behind their malignant behaviour and to identify new therapeutic strategies for their treatment. The authors conducted this study to explore potential targets for the treatment of colorectal GISTs (CRGISTs).
Methods In the current study, the authors focused on centromere protein F and survivin, two markers that are known to affect the malignant behaviour of other tumours. Expression of centromere protein F and survivin was detected through the immunohistochemical staining of paraffin-embedded tumour tissues and then scored. The relationship between the expression of the two markers and their clinical parameters was analysed. Associated Survival analysis was available based on follow-up information.
Results The authors demonstrated for the first time that centromere protein F and survivin expression were significantly associated with high risk and a poor prognosis (p<0.05) in CRGISTs. The authors also found that centromere protein F expression was more prevalent in males (p=0.002).
Conclusions The results suggest that centromere protein F and survivin are malignant behaviour markers for CRGISTs. The expression of centromere protein F or survivin points to a poor clinical outcome. Interfering with centromere protein F and/or survivin expression might be a potentially therapeutic strategy for treating malignant CRGISTs.
Gastrointestinal stromal tumours (GISTs) are rare tumours of the alimentary tract originating from mesenchymal tissues of the gastrointestinal tract, with mutations in c-KIT or platelet-derived growth factor receptor-α being observed most frequently. GISTs exhibit an unpredictable clinical course and are considered to have a similar malignancy potential in all patients, regardless of which risk grade they belonged to at primary diagnosis. Colorectal GISTs (CRGISTs), an independent cohort, were reported to have worse prognoses than the gastric GISTs. Limited studies have previously been performed to investigate potential mechanisms behind their malignant behaviour.
Centromere protein-F (CENP-F) is a transient kinetochore protein of approximately 350 kDa. Its expression increases in the G2 phase, but it is rapidly proteolysed at the end of mitosis. The distribution of CENP-F is limited to the kinetochore but not the centromere. It has been reported to play multiple roles in mitotic events, including centromere/kinetochore maturation, chromosome alignment and segregation, anaphase spindle stabilisation and proper chromosome biorientation. Overexpression of CENP-F has been detected in various human cancers, including head and neck cancers, breast cancers and non-Hodgkin's lymphomas.
Survivin, as a 16.3 kDa protein consisting of 142 amino acids, belongs to the inhibitor of apoptosis protein family and affects cell proliferation, angiogenesis and inhibition of apoptosis. The survivin gene is localised to human chromosome 17q25.3. Normally expressed in embryonic tissues, but not in normal adult tissues, the overexpression of survivin is detectable in a variety of human cancers. The relationship of survivin to tumourigenesis and poor prognosis in human colorectal cancer has been described by Kawasaki et al.
In this study, we examined the expression of CENP-F and survivin in tumour tissues from 46 colorectal GIST patients and evaluated the relationship of their expression with clinical parameters and prognoses. We demonstrated for the first time that CENP-F and survivin were associated with high risk and a poor prognosis in CRGISTs. Both CENP-F and survivin might be potential targets for gene therapy or protein interference in the treatment of CRGISTs.
Abstract and Introduction
Abstract
Aims Colorectal gastrointestinal stromal tumours (GISTs) are considered to be tumours with a relatively poor prognosis. Few reports have been performed to investigate the mechanisms behind their malignant behaviour and to identify new therapeutic strategies for their treatment. The authors conducted this study to explore potential targets for the treatment of colorectal GISTs (CRGISTs).
Methods In the current study, the authors focused on centromere protein F and survivin, two markers that are known to affect the malignant behaviour of other tumours. Expression of centromere protein F and survivin was detected through the immunohistochemical staining of paraffin-embedded tumour tissues and then scored. The relationship between the expression of the two markers and their clinical parameters was analysed. Associated Survival analysis was available based on follow-up information.
Results The authors demonstrated for the first time that centromere protein F and survivin expression were significantly associated with high risk and a poor prognosis (p<0.05) in CRGISTs. The authors also found that centromere protein F expression was more prevalent in males (p=0.002).
Conclusions The results suggest that centromere protein F and survivin are malignant behaviour markers for CRGISTs. The expression of centromere protein F or survivin points to a poor clinical outcome. Interfering with centromere protein F and/or survivin expression might be a potentially therapeutic strategy for treating malignant CRGISTs.
Introduction
Gastrointestinal stromal tumours (GISTs) are rare tumours of the alimentary tract originating from mesenchymal tissues of the gastrointestinal tract, with mutations in c-KIT or platelet-derived growth factor receptor-α being observed most frequently. GISTs exhibit an unpredictable clinical course and are considered to have a similar malignancy potential in all patients, regardless of which risk grade they belonged to at primary diagnosis. Colorectal GISTs (CRGISTs), an independent cohort, were reported to have worse prognoses than the gastric GISTs. Limited studies have previously been performed to investigate potential mechanisms behind their malignant behaviour.
Centromere protein-F (CENP-F) is a transient kinetochore protein of approximately 350 kDa. Its expression increases in the G2 phase, but it is rapidly proteolysed at the end of mitosis. The distribution of CENP-F is limited to the kinetochore but not the centromere. It has been reported to play multiple roles in mitotic events, including centromere/kinetochore maturation, chromosome alignment and segregation, anaphase spindle stabilisation and proper chromosome biorientation. Overexpression of CENP-F has been detected in various human cancers, including head and neck cancers, breast cancers and non-Hodgkin's lymphomas.
Survivin, as a 16.3 kDa protein consisting of 142 amino acids, belongs to the inhibitor of apoptosis protein family and affects cell proliferation, angiogenesis and inhibition of apoptosis. The survivin gene is localised to human chromosome 17q25.3. Normally expressed in embryonic tissues, but not in normal adult tissues, the overexpression of survivin is detectable in a variety of human cancers. The relationship of survivin to tumourigenesis and poor prognosis in human colorectal cancer has been described by Kawasaki et al.
In this study, we examined the expression of CENP-F and survivin in tumour tissues from 46 colorectal GIST patients and evaluated the relationship of their expression with clinical parameters and prognoses. We demonstrated for the first time that CENP-F and survivin were associated with high risk and a poor prognosis in CRGISTs. Both CENP-F and survivin might be potential targets for gene therapy or protein interference in the treatment of CRGISTs.