磷脂酰肌醇3激酶和磷酸化Akt在尖锐湿疣和宫颈鳞状细胞癌组织中的表达

Expressions of phosphatidylinositol 3 kinase and phosphorylated Akt in condyloma acuminatum andcervical squamous cell carcinoma

目的探讨磷脂酰肌醇3激酶（P13K）和磷酸化Akt（P—Akt）在尖锐湿疣和宫颈鳞状细胞癌发病中的作用。方法采用免疫组化和Western印迹法检测30例尖锐湿疣、30例宫颈鳞状细胞癌及15例正常人包皮组织中P13K和磷酸化Akt的表达，利用计算机图像采集与分析系统对免疫组化结果进行平均吸光度（A值）测定，并对免疫印迹测定结果进行灰度扫描。采用SPSSl7．0软件行t检验和方差分析。结果15例正常人皮肤中，仅表皮基底层可见P13K及P＇Akt阳性细胞；30例尖锐湿疣皮损中，P13K及P-Akt表达增强，表皮全层均可见阳性细胞；而30例宫颈鳞状细胞癌组织中P13K及P—Akt表达更强，明显高于尖锐湿疣，可见大量P13K及P—Akt强阳性细胞。免疫组化图像分析结果显示，宫颈鳞状细胞癌P13K和P—Akt表达（A值）分别为0．28±0．05和0．20±0．07，尖锐湿疣分别为0．22±0．04和0．17±0．03，正常人对照组分别为0．16±0．04和0．10±0．02，经方差分析，F值分别为44．87和20．64，P值均〈0．01。Western印迹结果与免疫组化检测一致，宫颈鳞状细胞癌P13K和P—Akt表达的相对灰度值分别为3．48±0．48和3．33±0．26，尖锐湿疣分别为1．99±0．11和1．96±0．11，正常人对照组分别为1．00±0．03和1．00±0．03，经方差分析，F值分别为354．83和302．33，P值均〈0．01。结论尖锐湿疣和宫颈鳞状细胞癌中P13K／Akt信号通路被异常激活，HPV有可能通过影响P13K和P—Akt的表达上调引起感染上皮的异常增殖。

Objective To investigate the roles ot phosphahdyhnos^tol 3 kmase （l^13K） and phosphorylated Akt （P-Akt） in the pathogenesis of cervical squamous cell carcinoma and condyloma acuminatum. Methods Immunohistochemistry and Western blot were used to detect the expressions of PI3K and P-Akt in tissue specimens from the lesions of 30 cases of cervical squamous cell carcinoma, 30 cases of condyloma acuminatum and the prepuce of 15 normal human controls. The average optical density and gray scale values were calculated and analyzed by t test and F test respectively. Results The expressions of PI3K and P-Akt were observed in only the basal layer of the epidermis of control specimens, but in the whole epidermis of condyloma acuminatum tissue specimens. Cervical squamous cell carcinoma tissue specimens displayed a stronger expression of PI3K and P-Akt compared with the control and condyloma acuminatum tissue specimens. As immunohistochemistry revealed, the average absorbance value for PI3K and P-Akt was 0.28 -＋ 0.05 and 0.20 ~ 0.07 respectively in cervical squamous cell carcinoma tissue specimens, 0.52 ＋- 0.04 and 0.17 _＋ 0.03 respectively in condyloma acuminatum tissue specimens, and 0.16 ＋ 0.04 and 0.10 ~ 0.02 respectively in the control tissue specimens; significant differences were observed in the expressions of PI3K and P-Akt among the three groups of tissue specimens （F = 44.87, 20.64, respectively, both P 〈 0.01）. The results of Western blot were consistent with those of immunohistochemistry, and there was a significant difference in the gray scale value for PI3K and P-Akt between cervical squamous cell carcinoma, condyloma acuminatum and control tissue specimens （3.48 -＋ 0.48 vs. 1.99 ＋ 0.11 vs. 1.00 ＋ 0.03, F= 354.83, P〈 0.01; 3.33 ＋ 0.26 vs. 1.96 ＋ 0.11 vs. 1.00 _＋ 0.03, F= 302.33, P〈 0.01）. Conclusions The PI3K/Akt signaling pathway is abnormally activated in condyloma acuminatum and cervical squamous cell carcinoma, and human papilloma virus may cause the abnormal proliferation of infected eDithelium likely bv affectinz the uorezulated expression of PI3K/P-Akt.