cFLIP在大肠癌组织中的表达及意义

Significance and Expression of cFLIP in Colorectal Carcinoma

目的检测细胞型FLICE抑制蛋白（cellular FLICE-like inhibitory protein，cFLIP）在大肠癌组织中的表达及其与临床病理特征的关系，初步探讨cFLIP在大肠癌发生、发展中的意义。方法用免疫组织化学法检测长型cFLIP（cFLIPL）在43例大肠癌及配对的正常大肠黏膜组织中的表达，根据染色细胞的比例，计算每张切片的“平均积分”，比较cFLIPL在大肠癌及配对正常黏膜组织中表达的差异，以及在大肠癌不同病理特征情况下cFLIPL表达的差异。结果cFLIPL不同程度地表达于正常大肠黏膜及腺癌组织中。cFLIPL主要表达于正常大肠黏膜及大肠癌细胞的细胞质，阳性细胞呈弥漫性分布。正常黏膜的cFLIPL表达积分范围为0-2．95分，平均积分（1．55±0．86）分；4．7％（2／43）未染色，为阴性表达（积分为0），20．9％（9／43）呈现较弱染色，为弱阳性表达（0〈积分≤1），74．4％（32／43）为阳性表达（积分范围为1．00-2．95）。cFLIPL在所有大肠腺癌组织中表达，积分范围为0．80-4．00分，平均积分（3．06±0．75）分，62．8％（27／43）的肿瘤呈cFLIPL强阳性表达（积分〉3分），34．9％（15／43）的肿瘤呈阳性表达（1〈积分≤3），只有1例为弱阳性（积分为0．80分）。72．1％（31／43）的腺癌呈cFLIPL高表达，25．6％（11／43）的腺癌呈cFLIPL正常表达，2．3％（1／43）的腺癌呈cFLIPL低表达。大肠癌cFLIPL的表达水平明显高于配对的正常黏膜组织，差异有统计学意义（P〈0．01）。但肝癌组织中cFLIPL的表达水平与Dukes分期、肿瘤分期、大体类型、组织学分型、淋巴结转移及肝转移均无关（P〉0．05）。结论cFLIPL在大肠癌组织中比在正常大肠黏膜中更强烈表达，这可能是在大肠癌恶性转化与进展过程中肿瘤细胞逃避凋亡的体内机理之一。

Objective To investigate the prevalence of cellular FLICE-like inhibitory protein （cFLIP） alterations in colorectal cancer and their possible implications for the progression of colorectal cancer. Methods The long type cFLIP （cFLIPL） was examined in 43 colorectal cancer specimens and the matched normal colorectal specimens by immunohistochemistry. Immunohistochemical staining for cFLIPL was assessed on an arbitrary semi-quantitative scoring system. Stained cells were counted under the magnification field （ × 100） and at least 20 fields per case were examined. Fields with non-stained cells were scored 0; fields with stained cells less than 5 % were scored 1; fields with stained cells from 5% to 25% were scored 2; fields with stained cells between 26% and 50% were scored 3, and fields with stained cells more than 50% were scored 4. According to the above schedule, a mean score of each specimen was calculated. Results cFLIPL protein expressions of variable intensity and extent were detected in the normal colorectal mucosa and adenocarcinomas, cFLIPL was mainly expressed in the cytoplasma. The positive cells were distributed in diffuse manner. The mean expression score in normal mucosa ranged from 0 to 2. 95 （mean score： 1.55±0.86）; 4.7%（2/43） of all cases were unstained and 20.9% （9/43） showed a weakly stained pattern （0〈mean score≤1） ; 74.4% （32/43） of all cases cFLIPL protein was expressed in all ad were positively stained （1.00〈mean score≤2.95）, respectively. and the score ranged from 0.80-4.00 （mean score： 3.06±0. 75） ; 62.8% （27/43） of the tumors examined were predominantly cFLIPL positive （mean score 〉3）, 34.9% （15/43） of the tumors were cFLIPL positive （1〈mean score≤3） and only one case was cFLIPL weakly positive （score： 0.80）. 72.1% （31/43） of adenocarcinomas expressed cFLIPL more intensely and extensively than matched normal colonic mucosa, cFLIPL expression of colorecthl cancer was significantly higher than that of matched normal mucosa, which was statistically significant （P〈0.01）. The extent of cFLIPL expression in tumors was independent of Dukes stage, tumor stage, gross type of tumor, histological type, or lymph and hepatic metastasis. Conclusion The expression level of cFLIPL in adenocarcinomas is much higher than that in matched normal mucosa. Overexpression of cFLIPL is a tumor-specific phenomenon, which can provide a selective growth advantage for colorectal cancer cells to escape from death receptor-mediated apoptosis.