食管鳞癌组织诱导型一氧化氮合酶和增殖细胞核抗原的表达及意义

目的探讨食管鳞癌组织诱导型一氧化氮合酶（iNOS）和增殖细胞核抗原（PCNA）的表达与食管癌临床病理因素的关系。方法用免疫组化法检测2009年1至4月山东省泰安市中心医院52例食管鳞癌组织和20例癌旁正常组织iNOS与PCNA的表达,计数PCNA标记指数（PCNA LI）。食管鳞癌组织及癌旁正常组织iNOS蛋白阳性表达率、PCNA LI比较分别采用χ2检验、t检验;食管癌组织iNOS阳性表达者与iNOS阴性表达者PCNA LI比较采用t检验;不同临床病理因素食管鳞癌组织iNOS蛋白表达、PCNA LI比较分别采用χ^2检验、t检验、方差分析,进一步两两比较采用SNK-q检验;食管鳞癌组织iNOS蛋白与PCNA蛋白表达的关联性分析采用χ^2检验。结果食管鳞癌组织iNOS阳性表达率、PCNA LI均高于癌旁正常组织,且差异均有统计学意义63.5%（33/52）与10.0%（2/20）比较,χ^2=14.455,P〈0.01;（53.29±14.55）与（2.65±1.82）比较,t=24.593,P〈0.05]。食管癌组织中,iNOS阳性表达者的PCNA LI高于iNOS阴性表达者,且差异有统计学意义（60.89±9.98）与（40.08±11.53）比较,t=6.842,P=0.000]。不同临床分期、分化程度、有无淋巴结转移患者的食管鳞癌组织iNOS蛋白表达差异有统计学意义（χ^2=9.372,P=0.025;χ^2=12.784,P=0.002;χ2=6.361,P=0.012）。随着食管鳞癌组织癌细胞分化程度的降低PCNA LI升高,中分化和低分化的食管鳞癌组织PCNA LI明显高于高分化的食管鳞癌（q=6.000、7.378,P均〈0.05）。有淋巴结转移的食管鳞癌组织PCNA LI高于无淋巴结转移的食管鳞癌组织,且差异有统计学意义（56.26±13.14）与（45.21±15.62）比较,t=2.556,P=0.014]。iNOS的表达与PCNA的表达有关联（χ^2=20.022,P=0.000）。结论 iNOS与PCNA蛋白在食管鳞癌组织中均有较高的阳性表达,且表达有关联。两者可能存在共同的激活机制,iNOS和PCNA蛋白表达与食管癌的恶性进程有关。

Expression and significance of inducible nitric oxide synthase and proliferating cell nuclear antigen in esophageal squamous cell carcinoma

Objective To investigate the expression of inducible nitric oxide synthase（ iNOS） and proliferating cell nuclear antigen（ PCNA） and the relationship with clinicopathologic parameter in esophageal squamous cell carcinoma. Methods Immunohistochemical method was used to detect the expression of iNOS and PCNA in 52 esophageal squamous cell carcinoma tissues and 20 paired para-carcinoma tissues from January to April in Taian City Central Hospital,and the PCNA labeling index（ PCNA LI） was counted. The iNOS expression rate and PCNA LI of the two groups were compared with χ2test and t test. PCNA LI of iNOS positive and negative esophageal squamous cell carcinoma tissues were compared with t test,The correlations between the expression of iNOS and PCNA LA and the clinical pathological features were analyzed with χ2test,t test and variance analysis,SNK-q test was used to do further comparation. The correlation between iNOS and PCNA in esophageal squamous cell carcinoma was analysed with χ2test. Results The positive expression rates of iNOS in esophageal squamous cell carcinoma and paired para-carcinama tissues were63. 5%（ 33 /52） and 10. 0%（ 2 /20）, and the difference was statistically significant（ χ2=14. 455,P 0. 01）. The PCNA LI in the two groups were 53. 29 ± 14. 55 and 2. 65 ± 1. 82,and the difference was statistically significant（ t = 24. 593,P 0. 05）. The PCNA LI in iNOS positive esophageal squamous cell carcinoma tissues was significantly higher than that in iNOS negative tissues （ 60. 89 ± 9. 98）vs（ 40. 08 ± 11. 53）; t = 6. 842,P = 0. 000]. There were significant differences among different groups（ according to clinical stage,differentiated degree and lymphatic metastasis） in the expression of iNOS（ χ2=9. 372,P = 0. 025; χ2= 12. 784,P = 0. 002; χ2= 6. 361,P = 0. 012）. The PCNA LI in moderate and poor differentiated tissues were significantly higher than that in well differentiated tissue（ q = 6. 600,7. 379,all P 0. 05）. PCNA LI in lymph node metastasis tissue was significantly higher than that in tissue without lymph node metastasis （ 56. 26 ± 13. 14） vs（ 45. 21 ± 15. 62）; t = 2. 556,P = 0. 014]. The expression of iNOS was positively correlated with that of PCNA（ χ^2= 20. 022,P = 0. 000）. Conclusions iNOS and PCNA are highly expressed and correlated in esophageal squamous cell carcinoma. It is speculated that a common activation mechanism may coexists between the two genes. The expressions of iNOS and PCNA play an important role in the malignant progression of esophagus carcinoma.