IGF-ⅡmRNA、bcl-2蛋白在结肠直肠腺癌组织中的表达及临床意义

背景与目的胰岛素样生长因子-Ⅱ(Insulin-likegrowthfactorⅡ,IGF-Ⅱ)能促进细胞分裂、增殖,B细胞淋巴瘤-2(bcl-2)蛋白能明显抑制细胞的凋亡,使细胞寿命延长.近来发现两者在结肠直肠癌中均存在过表达,但两者在结肠直肠癌中的联合检测尚未见报道.本文通过观察结肠直肠腺癌中IGF-ⅡmRNA、bcl-2蛋白的表达情况,结合肿瘤中细胞增殖和凋亡状态的研究,探讨IGF-Ⅱ,bcl-2基因表达的相关性以及与结肠直肠腺癌浸润、转移的关系,并探求两者联合检测的临床意义.方法选取48例结肠直肠腺癌石蜡标本,采用原位分子杂交检测IGF-ⅡmRNA,S-P法检测bcl-2蛋白,增殖细胞核抗原(PCNA),TUNEL法检测细胞凋亡,多媒体图文分析系统定量肿瘤阳性细胞率.以10例正常结肠直肠组织作为对照.结果结肠直肠腺癌中IGF-ⅡmRNA,bcl-2蛋白阳性细胞率[(38.70±7.80)%和(30.97±7.40)%]均显著高于正常结肠直肠组织[(23.12±4.07)%和(12.69±1.31)%](P<0.01),IGF-ⅡmRNA和bcl-2蛋白表达呈负相关(P<0.05),且均与肿瘤Dukes′分期有关和淋巴结转移有关,而与患者的年龄,性别,肿瘤大小,部位,分化程度无关.IGF-ⅡmRNA与PCNA,细胞凋亡显著正相关(P<0.01),bcl-2蛋白与细胞凋亡显著负相关(P<0.01),而与PCNA表达无关(P>0.05).IGF-ⅡmRNA阳性而bcl-2蛋白阴性者预后最差.结论结肠直肠腺癌中IGF-Ⅱ,bcl-2的过表达共同参与了肿瘤的发生,发展,浸润,转移,两者联合检测有一定的临床意义.

Expression and clinical significance of IGF-II mRNA and bcl-2 protein in colorectal adenocarcinomas

BACKGROUND & OBJECTIVE: Insulin-like growth factor II (IGF-II) can stimulate cell proliferation; B cell lymphoma 2 (bcl-2) protein can strongly inhabit cell apoptosis. Recently, the overexpression of IGF-II and bcl-2 in colorectal cancer has been found, but the combined detection of them has not been reported. The objective of this study was to investigate the relationship between the expression of IGF-II, bcl-2 and the invasion, metastases of colorectal adenocarcinomas and to analyze the clinical significance of combined detection of these factors. METHODS: Forty-eight paraffin embedded samples from colorectal adenocarcinomas were selected. IGF-II mRNA was detected by using in situ hybridization. The expression of bcl-2 and PCNA protein were determined immunohistochemically, and TUNEL technique was used to detect apoptosis. Ten normal colorectal tissues were used as controls. The positive cell ratio of cancers was calculated by computer. The specimens with positive cell ratio < or = 30% were defined as negative. RESULTS: The expressions of IGF-II mRNA and bcl-2 protein were significantly higher in colorectal adenocarcinomas (38.70% +/- 7.80% and 30.97% +/- 7.40%) than in normal colorectal tissues(23.12% +/- 4.07% and 12.69% +/- 1.31%) (P < 0.01) and were related to Dukes' stage and lymph node metastases but were not associated with patient's age, gender, tumor site, tumor size and tumor differentiation. A negative correlation was observed between IGF-II mRNA and bcl-2 protein (P < 0.05). A positive correlation between IGF-II mRNA and PCNA, apoptosis as well as a negative correlation between bcl-2 and apoptosis were observed (P < 0.01). There was no correlation between bcl-2 and PCNA (P > 0.05). The patients with IGF-II mRNA (+) and bcl-2 (-) were regarded as the worst prognosis. CONCLUSION: The overexpression of IGF-II and bcl-2 in colorectal adenocarcinomas play an important role in the pathogenesis, progression, invasion, and metastases of the tumor. Determination of both IGF-II and bcl-2 expression would be helpful for decision making of adjuvant therapy.