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Reduced Fhit expression is associated with mismatch repair deficiency in human advanced colorectal carcinoma.

Andachi H, Yashima K, Koda M, Kawaguchi K, Kitamura A, Hosoda A, Kishimoto Y, Shiota G, Ito H, Makino M, Kaibara N, Kawasaki H, Murawaki Y - Br. J. Cancer (2002)

Bottom Line: Recently, it has been reported that the Fragile Histidine Triad gene may be a target of damage in a fraction of mismatch deficient tumours.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).Moreover, reduced Fragile histidine triad expression was significantly associated with absence of mismatch repair protein expression in the advanced colorectal carcinomas (P<0.0001).

View Article: PubMed Central - PubMed

Affiliation: Second 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.

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Representative results of Mlh1 and Msh2 immunostaining in human normal and carcinomatous colorectal tissues. A and B, Poorly-differentiated carcinoma cells (B) show no nuclear staining for Mlh1 while normal crypt epithelium (A) shows nuclear staining; (C) Normal crypt epithlium shows nuclear staining for Msh2; (D), Moderately-differentiated carcinoma cells show nuclear staining for Msh2
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fig2: Representative results of Mlh1 and Msh2 immunostaining in human normal and carcinomatous colorectal tissues. A and B, Poorly-differentiated carcinoma cells (B) show no nuclear staining for Mlh1 while normal crypt epithelium (A) shows nuclear staining; (C) Normal crypt epithlium shows nuclear staining for Msh2; (D), Moderately-differentiated carcinoma cells show nuclear staining for Msh2

Mentions: The expression of both Mlh1 and Msh2 proteins was without exception nuclear. In the normal mucosa, they were detected predominantly in the areas of active proliferation, such as the germinal centres of the lymphoid follicles and the lower portions of the normal colonic crypts (Figure 2A,CFigure 2


Reduced Fhit expression is associated with mismatch repair deficiency in human advanced colorectal carcinoma.

Andachi H, Yashima K, Koda M, Kawaguchi K, Kitamura A, Hosoda A, Kishimoto Y, Shiota G, Ito H, Makino M, Kaibara N, Kawasaki H, Murawaki Y - Br. J. Cancer (2002)

Representative results of Mlh1 and Msh2 immunostaining in human normal and carcinomatous colorectal tissues. A and B, Poorly-differentiated carcinoma cells (B) show no nuclear staining for Mlh1 while normal crypt epithelium (A) shows nuclear staining; (C) Normal crypt epithlium shows nuclear staining for Msh2; (D), Moderately-differentiated carcinoma cells show nuclear staining for Msh2
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376126&req=5

fig2: Representative results of Mlh1 and Msh2 immunostaining in human normal and carcinomatous colorectal tissues. A and B, Poorly-differentiated carcinoma cells (B) show no nuclear staining for Mlh1 while normal crypt epithelium (A) shows nuclear staining; (C) Normal crypt epithlium shows nuclear staining for Msh2; (D), Moderately-differentiated carcinoma cells show nuclear staining for Msh2
Mentions: The expression of both Mlh1 and Msh2 proteins was without exception nuclear. In the normal mucosa, they were detected predominantly in the areas of active proliferation, such as the germinal centres of the lymphoid follicles and the lower portions of the normal colonic crypts (Figure 2A,CFigure 2

Bottom Line: Recently, it has been reported that the Fragile Histidine Triad gene may be a target of damage in a fraction of mismatch deficient tumours.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).Moreover, reduced Fragile histidine triad expression was significantly associated with absence of mismatch repair protein expression in the advanced colorectal carcinomas (P<0.0001).

View Article: PubMed Central - PubMed

Affiliation: Second 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.

Show MeSH
Related in: MedlinePlus