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

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。

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

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%,P<0.05);significant difference was also seen between ACF and normal mucosa(P<0.05).Expression rate of FAS was not different between ACF with and without dysplasia(36.0%vs.31.9%, P>0.05).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.