Fhit expression in human gastric adenomas and intramucosal carcinomas: correlation with Mlh1 expression and gastric phenotype

Abstract

The fragile histidine triad (FHIT) gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumour suppressor gene involved in a variety of tumours, including gastric carcinomas. Recently, it has been reported that the FHIT gene may be a target of damage in some of mismatch-deficient tumours. To clarify further the role of the Fhit protein in gastric carcinogenesis, we investigated whether Fhit expression in early gastric neoplasia is associated with mismatch repair protein expression and cellular phenotype. Fhit, Mlh1 and phenotypic expression were evaluated immunohistochemically in 87 early gastric neoplasias, comprising 32 adenomas and 55 intramucosal carcinomas, resected by endoscopic mucosal resection therapy. Significant loss or reduction of Fhit expression was noted in four (12.5%) of the 32 adenomas and 21 (38.2%) of the 55 intramucosal carcinomas. The rate of abnormal Fhit expression was significantly higher in intramucosal carcinomas than in adenomas (P ¼ 0.021). Moreover, reduced Fhit expression was found to be significantly associated with loss of Mlh1 expression in early gastric neoplasia (P ¼ 0.0011). Furthermore, we also detected a significant association between reduced Fhit expression and gastric phenotype (P ¼ 0.0018). These results suggested that reduced Fhit expression occurs in the early stage of gastric carcinogenesis and could be correlated with a lack of Mlh1 expression and gastric phenotype.

Immunohistochemical assessment of Fhit protein expression in advanced gastric carcinomas in correlation with Helicobacter pylori infection and survival time.

“…Similarly, we found no relationship between the protein expression and Lauren's and Borman's classifications. These data are consistent with the findings obtained by other researchers [13,14,15]. Capuzzi et al [13] found no correlation between Fhit protein expression and Lauren's classification or the rest of parameters.…”

“…Moreover, no relationship was observed between LOH of the FHIT gene and lymph node involvement (pN), differentiation grade or invasion through veins. Moreover, LOH of the FHIT gene did not affect prognosis within various groups of patients according to Lauren's classification or important prognostic parameters such as invasion depth (pT) and lymph node involvement (pN) [11,14].…”

Factores genéticos y epigenéticos del cáncer gástrico

“…La ausencia de FHIT se considera un indicador de mal pronóstico en CG y se asocia con invasión y metástasis (Zhao et al 2005). La proteína esta ausente hasta en el 12,5% de los adenomas, en 38,2% de carcinomas gástricos intramucosos y >60% en CG avanzados (Capuzzi et al 2000, Kawaguchi et al 2004). …”

Loss of Fhit expression is associated with poorer survival in gastric cancer but is not an independent prognostic marker

“…The lack of Fhit expression has also been correlated with infection by Helicobacter pylori and epithelial dysplasia [23,26]. Lastly, loss of Fhit expression has also been suggested to be correlated with loss of expression of mismatch repair protein Mlh1 and may occur at an early stage in tumor progression [11].…”