Koda Masaharu, Yashima Kazuo, Kawaguchi Koichirou, Andachi Hironobu, Hosoda Akihide, Shiota Goshi, Ito Hisao, Murawaki Yoshikazu
Division of Medicine and Clinical Science, Faculty of Medicine, Tottori University, 36-1 Nishi-machi, Yonago 683-8504, Japan.
Cancer Lett. 2003 Sep 25;199(2):131-8. doi: 10.1016/s0304-3835(03)00385-9.
There is limited information on the molecular changes involved in the pathogenesis of gallbladder carcinoma (GBC). The Fragile Histidine Triad (FHIT) gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumor suppressor gene in a variety of human malignancies. Recent studies have suggested that Fhit inactivation can be a consequence of defects in mismatch repair proteins. We analyzed Fhit and Mlh1 protein expressions using immunohistochemical methods in 20 GBCs and three gallbladder adenomas (GBAs) to elucidate the role of Fhit protein in gallbladder carcinogenesis. In addition, we examined whether Fhit and Mlh1 protein expressions correlated with P53 expression and clinicopathological findings. Significant loss or reduction in Fhit expression was noted in nine (45%) of the GBCs and one of the GBAs. Loss of Mlh1 protein expression was detected in six (30%) of the GBCs and one of the GBAs. Reduced Fhit expression was significantly associated with the absence of Mlh1 protein expression in the GBCs and the GBAs (p=0.0186). P53 overexpression was present in 11 (55%) of the GBCs, but none of the GBAs. Fhit and Mlh1 protein expressions were not significantly associated with P53 expression and clinicopathological findings. These results suggested that reduced Fhit expression might be involved in the development of GBC and be correlated with Mlh1 expression.
关于胆囊癌（GBC）发病机制中涉及的分子变化的信息有限。脆性组氨酸三联体（FHIT）基因，包含位于染色体3p14.2的FRA3B脆性位点，是多种人类恶性肿瘤中的候选肿瘤抑制基因。最近的研究表明，Fhit失活可能是错配修复蛋白缺陷的结果。我们采用免疫组织化学方法分析了20例GBC和3例胆囊腺瘤（GBA）中Fhit和Mlh1蛋白的表达，以阐明Fhit蛋白在胆囊癌发生中的作用。此外，我们还检测了Fhit和Mlh1蛋白表达是否与P53表达及临床病理结果相关。在9例（45%）GBC和1例GBA中观察到Fhit表达显著缺失或降低。在6例（30%）GBC和1例GBA中检测到Mlh1蛋白表达缺失。在GBC和GBA中，Fhit表达降低与Mlh1蛋白表达缺失显著相关（p=0.0186）。11例（55%）GBC中存在P53过表达，但GBA中均未出现。Fhit和Mlh1蛋白表达与P53表达及临床病理结果无显著相关性。这些结果表明，Fhit表达降低可能参与了GBC的发生，并与Mlh1表达相关。
