Skip to main content
Article thumbnail
Location of Repository

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

By H Andachi, K Yashima, M Koda, K Kawaguchi, A Kitamura, A Hosoda, Y Kishimoto, G Shiota, H Ito, M Makino, N Kaibara, H Kawasaki and Y Murawaki

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

Topics: Genetics and Genomics
Publisher: Nature Publishing Group
OAI identifier: oai:pubmedcentral.nih.gov:2376126
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles

    Citations

    1. (1999). Abnormal Fhit expression in malignant and premalignant lesions of the cervix.
    2. (2001). Microsatellite instability and the clinicopathological features of sporadic colorectal cancer. Gut 48: 821–829 G e n e t i c s a n d G e n o m i c s
    3. (2002). MMR in colorectal carcinomas H Andachi et al ã
    4. (1996). The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t (3;8) breakpoint, is abnormal in digestive tract cancers. Cell 84: 587–597 Peltomaki P, Vasen HF

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.