乙酰肝素酶表达在食管鳞癌演发过程中的意义

Significance of Heparanase Expression in the Course of Esophageal Squamous Cell Cancer Evolution

目的:研究乙酰肝素酶(heparanase,Hpa)在食管正常粘膜和各级不典型增生组织中的表达,并与癌组织中Hpa表达进行对比。探索Hpa在食管鳞癌早期诊断、早期治疗中的应用价值。方法:采取胃镜下标本,包括正常食管鳞状上皮、不典型增生组织和原位癌,用免疫组化染色和RT-PCR方法研究Hpa表达情况,并且与术后食管鳞癌组织对比。结果:免疫组化结果显示,正常组织阳性率0.0%(0/20),食管Ⅰ级不典型增生组织阳性率20.0%(2/10),Ⅱ级不典型增生组织阳性率18.2%(2/11),Ⅲ级不典型增生组织阳性率63.6%(7/11),原位癌组织阳性率60.0%(9/15),食管鳞癌组织Hpa阳性率63.6%(35/55)。食管Ⅰ级不典型增生组织、Ⅱ级不典型增生组织Hpa阳性率与正常食管上皮无显著差异(P>0.05);食管鳞癌组织、原位癌组织和Ⅲ级不典型增生组织3组阳性率相互之间无显著差异(P>0.05);食管鳞癌组织、原位癌组织和Ⅲ级不典型增生组织Hpa阳性率均高于正常食管上皮(P<0.05)。合并计算Ⅰ级和Ⅱ级不典型增生组织阳性率为19.0%(4/21),与Ⅲ级不典型增生组织63.6%(7/11)比较,有显著差异(P=0.017)。RT-PCR结果显示,Hpa基因扩增产物为585bp。正常组织Hpa基因阳性率5.0%(1/20),食管Ⅰ级不典型增生组织阳性率16.7%(1/6),Ⅱ级不典型增生组织阳性率33.3%(2/6),Ⅲ级不典型增生组织阳性率75.0%(6/8),食管鳞癌组织Hpa阳性率72.7%(40/55)。食管Ⅰ级不典型增生组织、Ⅱ级不典型增生组织Hpa阳性率与正常食管上皮无显著差异(P>0.05);食管鳞癌组织和Ⅲ级不典型增生组织两组之间阳性率无显著差异(P>0.05);食管鳞癌组织、Ⅲ级不典型增生组织Hpa阳性率均高于正常食管上皮(P<0.05)。合并计算Ⅰ级和Ⅱ级不典型增生组织阳性率为25.0%(3/12),与Ⅲ级不典型增生组织75.0%(6/8)比较,有显著差异(P=0.040)。结论:Hpa明显上调发生于食管正常鳞状上皮向鳞癌演发过程中的Ⅲ级不典型增生阶段。

Objective：To explore the value of Hpa in early diagnosis and treatment of esophageal cancer. Methods：Tissues of stomach endoscope biopsy, including normal epithelium, atypical dysplasia tissue and carcinoma in situ were picked up. Hpa expression was detected by immonohistochemical stain and RT-PCR assay, then these data were compared with resected cancer tissues. Results： （1） The rate of Hpa stain in normal epithelium was 0.0%（0/20）, atypical dysplasia I was 20.0%（2/10）, atypical dysplasia Ⅱ was 18.2%（2/11）, atypicaldysplasia Ⅲ was 63.6%（7/11）, carcinoma insitu was 60.0%（9/15）, cancer tissue was 63.6%（35/55）. Through statistic testing, there was no difference among normal epithelium, atypical dysplasia I and atypical dysplasia Ⅱ（P〉0.05）. There was no difference among atypical dysplasia Ⅲ, carcinoma in situ and cancer tissue （P〉0.05）. The rates of atypical dysplasia Ⅲ, carcinoma in situ and cancer tissue were much higher than those of normal epi- thelium（P〈0.05）. Compared the combined rate of atypical dysplasia I and atypical dysplasia Ⅱ[19.0（4/21）] with dysplasia Ⅲ [63.6%（7/11）], there was significant difference between the two groups （P = 0.017）. （2） The Hpa gene band was 585bp. the rate of Hpa stain in normal epithelium was 5.0%（1/20）, atypical dysplasia I was 16.7%（1/6）, atypical dysplasia Ⅱ was 33.3%（2/6）, atypical dysplasia Ⅲ was 75.0%（6/8） and the cancer tissue was 72.7%（40/55）. There was no difference among normal epithelium, atypical dysplasia I and atypical dysplasia Ⅱ（P〉0.05）. There was no difference between atypical dysplasia Ⅲ and cancer tissue（P〉0.05）. The rates of atypical dysplasia Ⅲ and cancer tissue were much higher than those of normal epithelium（P〈0.05）. Compared the combined rate of atypical dysplasia I and atypical dysplasia Ⅱ[19.0% （4/21）] with dysplasia Ⅲ [63.6%（7/11）], there was significant difference between this two groups （P=0.040）. Conclusion：The expression of Hpa begin to be up-regulated in atypical dysplasia Ⅲ, which is no difference with carcinoma in situ and cancer tissues.