【作者】 朱辉； 王士杰； 王小玲； 丛庆文； 孟宪利； 张立玮；

【Author】 Zhu Hui Wang Shi-Jie Wang Xiao-Ling Cong Qing-Wen Meng Xian-Li Zhang Li-Wei The Fourth Hospital of Hebei medical university & Hebei provincial tumor hospital, Shijiazhuang, 050011, China

【机构】 河北医科大学第四医院暨河北省肿瘤医院胸外科；

【摘要】 目的:乙酰肝素酶(Heparanase,Hpa)为降解细胞外基质和基底膜主要成份——硫酸乙酰肝素蛋白多糖 (Heparin sulfate proteoglycans,HSPGs)的内糖苷酶,在多种恶性肿瘤的侵袭转移中发挥重要作用。食管癌前病变是食管上皮癌变过程的必经阶段,目前Hpa在食管各级癌前病变中的表达国内外尚未见报道。本研究旨在探索Hpa在食管正常粘膜和各级不典型增生组织中的表达,并和癌组织中的表达进行对比研究,以观察Hpa在食管鳞癌演发过程中的表达规律,进而探索Hpa在食管鳞癌早诊早治中的应用价值。方法:在河北医科大学第四医院门诊内镜检查时,经1．5％碘液染色指导,于食管粘膜可疑病变处所钳取组织作为研究标本。经病理证实不典型增生I级者10例,Ⅱ级11例,Ⅲ级11例, 原位癌15例,正常食管鳞状上皮20例,免疫组化染色研究Hpa 蛋白表达情况;其中正常食管鳞状上皮标本20例和不典型增生病变标本20例(I级为6例,Ⅱ级6例,Ⅲ级8例),RT- PCR方法研究Hpa基因表达情况。以上结果与另组55例术后食管鳞癌组织标本中Hpa蛋白和基因表达的情况进行对比。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级阳性率 18．2％(2／11),Ⅲ级阳性率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)。经统计检验,食管I级和Ⅱ级不典型增生组织的Hpa阳性率与正常食管上皮无显著差别(P>0．05);食管鳞癌组织、原位癌组织和Ⅲ级不典型增生组织三组之间阳性率相互无显著差别(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<0．01)。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,差异有显著意义(P< 0．05)。RT-PCR结果显示: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级阳性率33．3％(2／6),Ⅲ级阳性率75．O％(6／8),食管鳞癌组织 Hpa阳性率72．7％(40／55)。食管I级和Ⅱ级不典型增生组织的Hpa阳性率与正常食管上皮无显著差别(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别 (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<0．01)。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,差异有显著意义(P<0．05)。结论:食管Ⅲ级不典型增生组织与原位癌和进展期鳞癌组织中Hpa表达无明显差别,均高于正常食管上皮。食管Ⅲ级不典型增生组织中Hpa基因和蛋白阳性率高于I级和Ⅱ级。在食管鳞状上皮Ⅲ级不典型增生阶段,Hpa的基因和蛋白表达明显上调,提示Hpa可能是食管癌变早期的标示基因之一。更多还原

【Abstract】 Objective: Heparanase is a kind of endo-D-glucuronidase that degrades heparin sulfate proteoglycans, which is the mainly components of extra cellular matrix and basement membrane. Heparanase plays an important role in many kinds of malignant tumor’ s invasion and metastasis. Esophageal precancerous lesion is a necessary stage in course of esophageal squamous cell cancer evolution, but there have no reports on heparanase expression in esophageal precancerous lesions. This research is to explore the heparanase expression mode in esophageal normal epithelium and different grades atypical dyspiasia tissues, and compare them with cancer tissues. And to explore the value of heparanase in early diagnosis and treatment of esophageal cancer. Methods: Pick up tissues of stomach endoscope biopsy, including 20 normal epithelium tissues, 10 atypical dyspiasia I tissues, 11 atypical dyspiasia II tissues, 11 atypical dyspiasia HI tissues and 15 carcinoma in situ. Those are detected heparanase protein by immonohistochemical stain. All 20 normal epithelium tissues and part of atypical dyspiasia tissues (including 6 atypical dyspiasia I tissues, 6 atypical dyspiasia II tissues and 8 atypical dyspiasia III tissues) is used to detected heparanase gene by RT-PCR assay. And compare those data with 55 resected cancer tissues. Results: The result of immumohistochemical stain is: the rate of heparanase stain in normal epithelium is 0.0% (0/20), atypical dyspiasia I is 20.0%(2/10), atypical dyspiasia II is 18.2%(2/11), atypical dyspiasia III is 63.6%(7/11), carcinoma in situ is 60.0%(9/15), cancer tissue is 63.6%(35/55). Through statistic testing, there is no difference among normal epithelium, atypical dyspiasia I and atypical dyspiasia II (P > 0.05). There is no difference among atypical dyspiasia III, carcinoma in situ and cancer tissue(P > 0.05). The rates of atypical dyspiasia III, carcinoma in situ and cancer tissue are much higher than that of normal epithelium respectively(P < 0.01). Compared the combined rate of atypical dyspiasia I and atypical dyspiasia II 19.0(4/21) with dyspiasia III 63.6%(7/11), there is significant difference between the two groups (P < 0.05). The result of RT-PCR assay is: the rate of heparanase stain in normal epithelium is 5.0% (1/20), atypical dyspiasia I is 16.7%(l/6), atypical dyspiasia II is 33.3% (2/6), atypical dyspiasia III is 75.0%(6/8) and the cancer tissue is 72.7%(40/55). Through statistic testing, there is no difference among normal epithelium, atypical dyspiasia I and atypical dyspiasia II (P > 0.05). There is no difference between atypical dyspiasia III and cancer tissue(P > 0.05). The rates of atypi- cal dysplasia III and cancer tissue are much higher than that of normal epithelium respectively(P < 0.01). Compared the combined rate of atypical dysplasia I and atypical dysplasia II 19.0%(4/21) with dysplasia III 63.6% (7/11), there is significant difference between this two groups (P < 0.05). Conclusion: The expre更多还原