非小细胞肺癌中Axin与β-连环素异常表达的关系

目的 探讨Axin（axis inhibition protein）和β-连环素（β-catenin）在非小细胞肺癌（NSCLC）中的表达、β-catenin突变及它们与各临床病理因素的关系。方法 采用免疫组织化学（SP法）和直接测序方法对100例NSCLC标本中Axin和β-catenin的表达和β-catenin基因突变进行了检测。结果 β-catenin的细胞膜表达降低率为80．0％,细胞核表达率为26．0％。高、中分化和低分化NSCLC中,β-catenin的表达降低率分别为70．0％（35／50）和90．0％（45／50）,差异有统计学意义（P=0．012）。有淋巴结转移和无淋巴结转移NSCLC中β-catenin表达降低率分别为87．3％（48／55）和71．1％（32／45）,差异有统计学意义（P=0．044）。Axin的阳性表达率为48．0％,高、中分化和低分化NSCLC中,Axin的阳性率分别为60．0％（30／50）和36．0％（18／50）,差异有统计学意义（P=0．016）。在β-catenin核表达阳性的病例中,Axin阳性表达率为15．4％（4／26）,低于β-catenin核表达阴性的病例（59．5％,44／74）（P〈0．001）。100例肺癌新鲜标本中未发现β-catenin基因第三外显子突变。结论 β-catenin的膜表达降低与NSCLC的低分化和淋巴结转移相关,Axin的表达与NSCLC的低分化和β-catenin的细胞核蓄积负相关。β-catenin基因第三外显子的突变可能不是NSCLC中β-catenin蛋白异常表达的主要原因。

Expressions of Axin and beta-catenin in non-small cell lung cancer

OBJECTIVE: To investigate the protein expression of Axin and beta-catenin, the exon 3 mutation status of beta-catenin and their clinicopathological correlations in non-small cell lung cancer (NSCLC). METHODS: A total of 100 NSCLC samples and their corresponding normal lung tissues were obtained from the patients undergoing surgery in the First Affiliated Hospital of China Medical University between 2001 and 2003. Protein expressions of Axin and beta-catenin were detected by immunohistochemistry. DNA sequence alterations of exon 3 of beta-catenin were investigated by polymerase chain reaction (PCR) and direct sequencing. RESULTS: A reduced membranous expression rate of beta-catenin was observed in 80.0% of the cases (80/100) along with a nuclear expression rate of 26.0% (26/100). There was a significant difference in beta-catenin expression between well and poorly differentiated NSCLCs. Well to moderately differentiated NSCLCs showed a reduced expression rate of 70.0% (35/50), in contrast to 90.0% (45/ 50) in poorly differentiated tumors (P = 0.012). Reduced beta-catenin expression rate was 87.3% (48/55) in cases with lymph node metastasis, in contrast to 71.1% (32/45) in cases without lymph node metastasis (P = 0.044). The positive expression rate of Axin was 48.0% (48/100). Well to moderately differentiated NSCLCs demonstrated a 60.0% positive expression rate of Axin (30/50), much higher than poorly differentiated tumors [36.0% (18/50), P = 0.016]. The positive expression rate of Axin in beta-catenin nuclear expressed NSCLCs was 15.4% (4/26), much lower than cases without beta-catenin nuclear expression [59.5% (44/74), P < 0.001]. Axin nuclear expression was found in two cases in this study, suggesting that it may function as a nuclear-cytoplasmic shuttling protein. PCR and direct sequencing failed to reveal any exon 3 mutation of beta-catenin gene. CONCLUSIONS: The reduced membranous expression of beta-catenin is associated with poorly differentiated and lymph node positive NSCLCs. The expression of Axin is inversely correlated with the degree of tumor differentiation and nuclear expression of beta-catenin. The exon 3 mutations do not contribute to the abnormal protein expression of beta-catenin in NSCLCs.