肿瘤抑制基因、磷酸化AKT、细胞周期素D1在肺鳞癌和腺癌中不同的表达及与临床病理因素的相关性

Expression and relationship of PTEN, phosphor-AKT and Cydin D1 in lung squamous cell carcinoma and lung adenocarcinoma

目的探讨AKT信号转导通路中有关蛋白肿瘤抑制基因（PTEN）、磷酸化AKT（p-AKT）及细胞周期素D1（CyclinD1）在原发性肺鳞癌和腺癌中不同的表达意义及与临床病理因素的相关性。方法应用免疫组化的方法，检测原发性肺鳞癌44例、腺癌36例及35例非肿瘤性肺组织标本中PTEN、p-AKT、CycllnD1的表达，并与临床病理因素进行相关性分析。结果p-AKT、CyclinD1在肺鳞癌和腺癌中总的阳性率分别为78．8％、76．3％，均显著高于非肿瘤性肺组织中阳性表达0％（均P〈0．05）。PTEN在肺鳞癌和腺癌中总阳性率为47．5％，显著低于非肿瘤性肺组织中阳性表达94．3％（P〈0．05）。PTEN、P—AKT、CycllnD1在肺鳞癌和腺癌中的表达差异均无统计学意义（均P〉0．05）。PTEN表达与有无淋巴结转移和组织的高分化有关。p-AKT在高中分化腺癌中阳性表达显著高于低分化腺癌的表达。CyclinD1表达与淋巴结转移、鳞癌的低分化有关。在肺鳞癌和腺癌中，p-AKT蛋白的表达均与CyclinD1呈正相关。肺鳞癌中，PTEN表达与P，AKT、CyclinD1呈负相关；肺腺癌中，PTEN表达与p-AKT、CyclinD1均无相关关系。结论在肺鳞癌和腺癌中均存在AKT及其通路的激活。PTEN的失活参与了肺鳞癌和腺癌的发生和发展。在肺鳞癌中，AKT的激活与PTEN的失活有关；在肺腺癌中，PTEN的失活可能不是AKT活化的主要原因。在肺鳞癌和腺癌中可能存在不同的AKT活化机制。

Objective To investigate the expression,clinical significance and relationship of PTEN,phos- pho-AKT（p-AKT） and Cyclin D1 in human lung squamous cell carcinoma and lung adenocarcinoma tissue. Meth- ods The expression of PTEN, p-AKT, Cyclin D1 in 80 cases of lung squamous cell carcinoma and lung adenocarcinoma tissue and 35 cases of non-cancerous lung disease were assessed by immunohistochemistry, and their correlations with clinicopathologic factors were statistically analyzed. Results The total positive rate of p-AKT, Cyclin D1 was 78.8% and 76.3% in lung squamous cell carcinoma and adenocarcinoma and 0% in no-cancerous lung disease （P 〈0.05）. But the positive rate of PTEN was significandy lower in cancerous tissue（47.5% ） than that in noncancerous lung disease （94.3%）. No difference was observed between the positive rate of PTEN,p-AKT,Cyclin D1 in lung squamous cell carcinoma and lung adenocarcinoma. The expression of PTEN was correlated with lymph node metastasis and highly differentiation of cancer tissues. The positive rates of p-AKT in well-differentiated and moderately-differentiated adenocarcinoma were significantly higher than that of p-AKT in poorly-differentiated adenocarci- noma. The expression of Cyclin D1 was correlated with lymph node metastasis and differentiation of squamous cell carcinoma. In addition,the expression of p-AKT had positive correlation with the expression of Cyclin D1 in lung squamous cell carcinoma and lung adenocarcinoma. The expression of PTEN had negative correlation with the expression of p-AKT and Cyclin D1 in lung squamous cell carcinoma. No correlations were observed between the expression of PTEN and p-AKT, Cyclin D1 in lung adenocarcinoma. Conclusion AKT activation and its signaling pathway may be present in lung squamous cell carcinoma and lung adenocarcinoma. The loss of PTEN expression may participate in carcinogenesis and development of lung squamous cell carcinoma and lung adenocarcinoma. AKT activation may correlate to the loss PTEN expression in lung squamous cell carcinoma. The loss of PTEN may not be the reason of activation of AKT. The different AKT activation mechanism may exist in lung squamous cell carcinoma and lung adenocarcinoma.