散发性结直肠癌组织中FHIT、MSH2蛋白的异常表达及其临床意义

Abnormal Expression of Fragile Histidine Triad (FHIT) and Mut S Homolog 2 (MSH 2) Proteins in Human Sporadic Colorectal Carcinoma and Their Clinical Significance

背景与目的:脆性组氨酸三联体(fragilehistidinetriad,FHIT)蛋白表达缺失是胃肠道肿瘤的频发事件,但在大肠癌却有争议;最近研究表明FHIT蛋白表达失活可能是错配修复蛋白,尤其是mutS同种组织蛋白2(mutShomolog2,MSH2)改变的结果。本研究旨在探讨FHIT、MSH2蛋白在散发性结直肠癌(sporadiccolorectalcarcinoma,SCC)组织中的表达情况及其临床意义。方法:采用免疫组化SP法检测手术切除的84例SCC及其对应癌旁正常结直肠组织和23例肠腺瘤组织标本中FHIT、MSH2蛋白的表达。结果:FHIT蛋白在SCC组织、结直肠腺瘤组织、癌旁正常结直肠组织中阳性率分别为48.81%、73.91%和100%,三者的阳性率差异有显著性(P<0.05)。FHIT蛋白表达水平与SCC患者的年龄、性别及肿瘤部位、组织学类型无关(P>0.05),而与肿瘤浸润深度、分化程度、Dukes分期和淋巴结转移有关(P<0.05),在浸润深度越深、分化程度越低、Dukes分期越晚和有淋巴结转移的癌组织中,FHIT蛋白低表达就越明显;而MSH2蛋白表达水平仅与Dukes分期有关(P<0.05)。SCC中FHIT蛋白表达与MSH2蛋白表达呈正相关(r=0.3728,P<0.01)。结论:(1)FHIT蛋白表达水平与SCC的恶性程度有关,可作为预测SCC浸润转移潜能的一项有意义的生物学指标;(2)SCC中FHIT、MSH2蛋白表达二者之间呈正相关。

BACKGROUND & OBJECTIVE: Frequent loss of fragile histidine triad (FHIT) expression in human gastrointestinal tract carcinomas has been reported; however, there were divergent opinions regarding FHIT expression in colorectal c arcinoma. Recent studies have suggested that FHIT inactivation can be a conseque nce of defects in mismatch repair proteins, particularly mut S homolog 2 (MSH2). This study was designed to investigate the expression and clinical significance of FHIT and MSH2 proteins in human sporadic colorectal carcinoma (SCC). METHODS : Immunohistochemistry SP method was used to determine the expression of FHIT an d MSH2 in surgically resected specimens of 84 SCC and its corresponding paratumo r normal colorectal tissues, and 23 cases of colonic adenomas. RESULTS: The posi tive expression rates of FHIT protein were 48.81%, 73.91%, and 100% in SCC, colonic adenomas, and adjacent normal colorectal tissues, respectively. The posi tive expression rates of FHIT protein showed increasing trend from SCC, colonic adenomas, to paratumor normal colorectal tissues; and the difference was statist ically significant (P< 0.05). The expression levels of FHIT were not associated with age, gender, tumor site, and histological type (P >0.05), but were correlat ed with tumor invasive depth, differentiation degree, Dukes,stage, and lymph no de metastasis (P< 0.05). The tumor tissues of deeper invade depth, lower differentiation degree, later Ducks,stage and with lymph node metastasis showe d more reduction of FHIT protein expression. The expression level of MSH2 was on ly related to Dukes, stage (P< 0.05). FHIT expression was closely associate d with MSH2 expression in SCC (r=0.3728,P< 0.01). CONCLUSION: (1) Loss or reduct ion of FHIT protein expression plays an important role in the development and pr ogression of SCC. The expression levels of FHIT protein are related to the malig nant degree of SCC and may be a valuable biological indicator for predicting the potent invasion and metastasis of SCC. (2) FHIT protein expression is in a posi tive correlation fashion with MSH2 protein expression in SCC.