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目的分析胎儿食管上皮发育与成人食管上皮癌(esophagealcarcer,EC)癌变多阶段演进过程中p16,PCNA表达的变化。方法采用卵白素-生物素-辣根过氧化物酶复合物法和RT-PCR方法比较不同胎龄(3~5月18例,6~9个月8例)食管上皮和67例正常成人食管上皮、56例基底细胞增生、36例不典型增生、44例高分化、22例低分化食管鳞癌癌组织中p16和PCNA蛋白和mRNA表达变化特征。结果随胎儿胎龄增加,p16和PCNA蛋白表达呈升高趋势。但成人食管正常上皮p16阳性表达率较高,随病变程度加重,p16蛋白阳性表达率逐渐下降;而PCNA蛋白与此相反,随病变程度加重,PCNA蛋白阳性率均明显升高。高分化食管癌组织p16蛋白阳性表达率明显高于低分化食管癌组织(32%vs9%,χ2=13.426,P<0.05)。胎儿食管上皮发育和成年人食管上皮癌变过程中的p16和PCNAmRNA表达与上述蛋白表达特点相似,即随胎龄增加,p16和PCNAmRNA表达均呈升高趋势,而高分化食管癌组织p16mRNA表达明显高于低分化食管癌组织(68%vs32%,χ2=32.059,P<0.05),PCNAmR-NA表达与此相反(11%vs59%,χ2=28.647,P<0.05)。结论胎儿食管上皮发育过程中和成人食管上皮癌变过程中均出现不同程度的p16和PCNA表达,这种不同基因的表达变化可能是导致不同分化结局的分子机制之一。
Objective To analyze the changes of fetal esophageal epithelial development and the progression of p16 and PCNA expression in esophageal carcinoma (EC) during multistage progression. Methods Different gestational ages (18 cases in 3 to 5 months and 8 cases in 6 to 9 months) were compared between the esophageal epithelium and 67 cases of normal adult esophagus using the avidin-biotin-horseradish peroxidase complex method and RT-PCR method. Epithelial, 56 cases of basal cell hyperplasia, 36 cases of atypical hyperplasia, 44 cases of well-differentiated, 22 cases of poorly differentiated esophageal squamous cell carcinoma tissue and p16 and PCNA protein and mRNA expression changes. Results With the increase of fetal gestational age, the expression of p16 and PCNA protein increased. However, the positive expression rate of p16 in normal human esophageal epithelium was higher, and the positive expression rate of p16 protein gradually decreased with the severity of the disease. However, contrary to the PCNA protein, the positive rate of PCNA protein was significantly increased with the severity of the disease. The positive expression rate of p16 protein in well-differentiated esophageal carcinoma was significantly higher than that in poorly-differentiated esophageal carcinoma (32% vs 9%, χ2=13.426, P<0.05). The expression of p16 and PCNA mRNA during fetal esophageal epithelial development and adult esophageal epithelial carcinogenesis is similar to the above-mentioned protein expression. That is, with the increase of gestational age, the expression of p16 and PCNA mRNA both show an upward trend, while the expression of p16 mRNA in well-differentiated esophageal cancer tissue is significantly higher. In poorly differentiated esophageal cancer tissue (68%vs32%, χ2=32.059, P<0.05), PCNAmR-NA expression was the opposite (11% vs 59%, χ2=28.647, P<0.05). Conclusion The expressions of p16 and PCNA are different in fetal esophageal epithelial development and adult esophageal epithelial carcinogenesis. The expression of these different genes may be one of the molecular mechanisms leading to different differentiation outcomes.