Related Experiment Video
Updated: Sep 30, 2026
Deficient Pms2, ERCC1, Ku86, CcOI in Field Defects During Progression to Colon Cancer
Published on: July 28, 2010
Reduced Fhit expression is associated with mismatch repair deficiency in human advanced colorectal carcinoma
1Second Department of Internal Medicine, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan.
Abstract:
The Fragile Histidine Triad gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumour suppressor gene involved in multiple tumour types including colorectal carcinomas. Recently, it has been reported that the Fragile Histidine Triad gene may be a target of damage in a fraction of mismatch deficient tumours. To explore this hypothesis, we analysed both Fragile histidine triad and mismatch repair protein (Msh2 and Mlh1) expression using immumohistochemical methods in 52 advanced colorectal carcinomas (19 well-, 17 moderately-, and 16 poorly-differentiated). In addition, we examined whether the Fragile histidine triad and mismatch repair protein expression correlated with p53 expression and clinicopathological findings. Significant loss or reduction of Fragile histidine triad expression was noted in 18 of the 52 (34.6%) advanced colorectal carcinomas: 2 (10.5%) well-differentiated, 3 (17.6%) moderately-differentiated, 13 (81.3%) poorly-differentiated carcinomas, the frequency being significantly higher in the latter than that in the former two (P<0.0001). Loss of mismatch repair protein (mainly, Mlh1) expression was detected in 21 of the 52 (40.4%) colorectal carcinomas. Moreover, reduced Fragile histidine triad expression was significantly associated with absence of mismatch repair protein expression in the advanced colorectal carcinomas (P<0.0001). However, the Fragile histidine triad and mismatch repair protein expression was not significantly associated with p53 expression. These results suggested that reduced Fragile histidine triad expression might be correlated with mismatch repair expression, but not with p53 expression.
Insights
Reduced Fragile Histidine Triad gene expression is common in advanced colorectal carcinomas, particularly in poorly-differentiated types. This loss often correlates with mismatch repair deficiency, suggesting a link in tumor development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The Fragile Histidine Triad (FHIT) gene is a candidate tumor suppressor implicated in various cancers, including colorectal carcinomas.
- Recent findings suggest FHIT may be affected in mismatch repair-deficient (dMMR) tumors.
- Understanding FHIT's role in colorectal cancer progression and its relationship with DNA repair mechanisms is crucial.
Purpose of the Study:
- To investigate the expression of the Fragile Histidine Triad (FHIT) gene in advanced colorectal carcinomas.
- To determine the correlation between FHIT expression and mismatch repair (MMR) protein expression (Msh2, Mlh1).
- To examine the association of FHIT and MMR protein expression with p53 expression and clinicopathological features.
Main Methods:
- Immunohistochemical analysis of FHIT, Msh2, and Mlh1 protein expression in 52 advanced colorectal carcinoma samples.
- Categorization of tumors based on differentiation: well-, moderately-, and poorly-differentiated.
- Statistical analysis to assess correlations between protein expression, p53 status, and clinicopathological data.
Main Results:
- Significant loss or reduction of FHIT expression was observed in 34.6% of colorectal carcinomas, predominantly in poorly-differentiated tumors (81.3%).
- Loss of MMR protein expression (primarily Mlh1) was detected in 40.4% of the cases.
- Reduced FHIT expression was significantly associated with the absence of MMR protein expression (P<0.0001).
Conclusions:
- Reduced FHIT expression is frequent in advanced colorectal carcinomas and strongly linked to mismatch repair deficiency.
- The findings suggest a potential interplay between FHIT and MMR pathways in colorectal tumorigenesis.
- FHIT and MMR protein expression were not significantly associated with p53 expression in this cohort.
Related Concept Videos
01:20Mismatch Repair
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
01:48Mismatch Repair
02:23Abnormal Proliferation
02:31Homologous Recombination