结肠癌患者直肠异型隐窝灶中脂肪酸合成酶的表达及其意义

Expression and Significance of Fatty Acid Synthase in Rectal Aberrant Crypt Foci in Patients with Colon Cancer

背景:异型隐窝灶(ACF)是结直肠上皮性肿瘤最早期的形态学改变,可经腺瘤进展至结直肠癌。脂肪酸合成酶(FAS)在多数人恶性肿瘤组织中呈高表达。目的:检测结肠癌患者直肠ACF中的FAS表达情况,探讨ACF中FAS表达异常在结直肠癌形成中的意义。方法:30例确诊的散发性结肠癌患者纳入研究。以0.2%亚甲蓝溶液行直肠黏膜染色,通过放大结肠镜寻找、识别ACF,选取隐窝数目超过30个的较大的ACF为研究对象。以免疫组化染色检测直肠ACF以及配对结肠癌组织和正常结肠组织中的FAS表达。结果:30例结肠癌患者共确定116个目标ACF,不伴异型增生91个,伴异型增生25个。结肠癌组织中的FAS阳性表达率显著高于ACF和正常结肠组织(76.7%对32.8%和10.0%,P<0.05),ACF与正常结肠组织间差异亦有统计学意义(P<0.05)。伴异型增生的ACF FAS阳性表达率与不伴异型增生者无明显差异(36.0%对31.9%,P>0.05)。结论:F.AS在结直肠癌腺瘤-癌发生序列的最早期即已出现表达异常,在结直肠癌的形成中发挥重要作用。以FAS抑制剂抑制ACF进展可能成为结直肠癌化学预防的手段之一。

Background：Aberrant crypt foci（ACF） is the earliest morphological precursor of epithelial neoplasia in colorectum, which may progress through adenoma to carcinoma.Fatty acid synthase（FAS） is highly expressed in most human carcinomas.Aims：To investigate the expression of FAS in rectal ACF in patients with colon cancer,and to study the significance of FAS overexpression in ACF in the pathogenesis of colorectal cancer.Methods：Thirty patients with sporadic colon cancer confirmed pathologically were enrolled in this study.The rectal mucosa was stained with 0.2% methylene blue and ACF was identified by magnifying colonoscopy.Large ACF（30 crypts/focus） was selected and biopsied.Expression of FAS in rectal ACF and paired colon cancer tissue and normal colonic mucosa was determined by immunohistochemistry.Results：A total of 116 large ACF were selected and biopsied in 30 colon cancer patients,25 with dysplasia and 91 without dysplasia.Colon cancer tissue had a significantly higher positivity rate for FAS than ACF and normal mucosa（76.7%vs.32.8%and 10.0%,P0.05）;significant difference was also seen between ACF and normal mucosa（P0.05）.Expression rate of FAS was not different between ACF with and without dysplasia（36.0%vs.31.9%, P0.05）.Conclusions：FAS overexpression occurs early and plays an important role in the adenoma-carcinoma sequence of colorectal cancer.Inhibiting the progression of ACF by FAS inhibitors may provide an approach for chemoprevention of colorectal cancer.