Kuwai Toshio, Tanaka Shinji, Kaio Eijiro, Hiyama Toru, Ito Masanori, Kitadai Yasuhiko, Sumii Masaharu, Yoshihara Masaharu, Haruma Ken, Chayama Kazuaki
Department of Medicine and Molecular Science, Division of Frontier Medical Science, Hiroshima University, Graduate School of Biomedical Sciences, Hiroshima, Japan.
Int J Mol Med. 2003 Oct;12(4):437-42.
It is unclear how expression of the FHIT (fragile histidine triad) gene by the colorectal neoplasm correlates with histogenesis and progression of the disease. We studied the association between expression of Fhit protein and development of colorectal carcinoma (CRC). We also examined relations between Fhit protein expression, macroscopic type, Ki-67 labeling index (LI), and p53 overexpression in carcinoma in situ. We examined 27 colorectal adenomas, 82 carcinomas in situ and 21 invasive CRCs resected endoscopically or surgically. The carcinomas in situ comprised three macroscopic types: polypoid (n=27), superficial (flat elevated, n=27; depressed, n=10) and granulonodular laterally spreading tumor (G-LST, n=23). Fhit, Ki-67, and p53 overexpression were examined immunohistochemically. Levels of Fhit protein were lower in invasive CRC than in adenoma and carcinoma in situ (p<0.01). In carcinoma in situ, reduced Fhit expression was observed in 7 of 22 (31.8%) polypoid types, 13 of 27 (48.1%) superficial flat elevated types, 8 of 10 (80%) superficial depressed types and 7 of 23 (30.4%) G-LST. Frequencies of reduced Fhit expression were significantly higher in the polypoid type and G-LST lesions than in the depressed type (p<0.05). Reduced expression of Fhit protein was related significantly to Ki-67 LI and p53 overexpression in carcinoma in situ (p<0.01). The present findings suggest that reduced expression of Fhit protein is related to development of colorectal neoplasm. Polypoid CRC and G-LST appear to differ from superficial depressed CRC in terms of Fhit expression.
尚不清楚结肠直肠肿瘤中FHIT（脆性组氨酸三联体）基因的表达与该疾病的组织发生及进展如何相关。我们研究了Fhit蛋白表达与结肠直肠癌（CRC）发生之间的关联。我们还检查了原位癌中Fhit蛋白表达、大体类型、Ki-67标记指数（LI）和p53过表达之间的关系。我们检查了27例结肠直肠腺瘤、82例原位癌和21例经内镜或手术切除的浸润性CRC。原位癌包括三种大体类型：息肉样（n = 27）、表浅型（扁平隆起型，n = 27；凹陷型，n = 10）和颗粒结节型侧向扩散肿瘤（G-LST，n = 23）。采用免疫组织化学方法检测Fhit、Ki-67和p53过表达情况。浸润性CRC中Fhit蛋白水平低于腺瘤和原位癌（p<0.01）。在原位癌中，22例息肉样类型中有7例（31.8%）、27例表浅扁平隆起型中有13例（48.1%）、10例表浅凹陷型中有8例（80%）以及23例G-LST中有7例（30.4%）观察到Fhit表达降低。息肉样类型和G-LST病变中Fhit表达降低的频率显著高于凹陷型（p<0.05）。原位癌中Fhit蛋白表达降低与Ki-67 LI及p53过表达显著相关（p<0.01）。目前的研究结果表明，Fhit蛋白表达降低与结肠直肠肿瘤的发生有关。息肉样CRC和G-LST在Fhit表达方面似乎与表浅凹陷型CRC不同。
