宫颈癌组织AKT和P-AKT表达与LMVD相关性及其对新辅助化疗效果预测意义

目的 宫颈癌新辅助化疗(neoadjuvant chemotherapy,NACT)的疗效一直存在争议,PI3K/AKT通路在肿瘤细胞增殖、迁移、侵袭及抗凋亡都起到举足轻重的作用.本研究探讨NACT对宫颈鳞状细胞癌AKT通路中AKT及P-AKT的表达对肿瘤微淋巴管生成的影响,并分析其变化与NACT临床疗效的关系.方法 采用免疫组化SP法分别检测2011-03-01-2016-03-31滨州医学院附属医院收治的47例 ⅠB2~ⅡB期宫颈鳞癌患者行NACT前后AKT和P-AKT的表达情况及肿瘤微淋巴管密度(lymphatic microvessel density,LMvD)的变化.结果 免疫组化检测结果显示,NACT前AK和P-AKT的阳性率分别为93.6%和72.3%,化疗后阳性率分别为44.7%和36.2%,NACT前后比较,AKT和P-AKT表达差异有统计学意义,P<0.001.化疗前宫颈鳞癌组织中LMvD计数为20.87±3.31,化疗后宫颈鳞癌组织中LMvD计数为16.47±3.44,化疗后宫颈鳞癌组织中LMvD明显降低,t=6.32,P<0.001.化疗前宫颈鳞癌AKT阳性的LMvD为21.14±3.19,高于阴性组(17.00±3.00).Spearman相关分析显示,化疗前后LMvD的表达(rs=0.39,P=0.007)与化疗前后P-AKT的表达(rs=0.66,P<0.001)均呈正相关.化疗后LMvD与化疗后AKT的表达呈正相关,rs=0.58,P<0.001.淋巴结转移与化疗前后LMvD均呈正相关(rs=0.44,P<0.001;rs=0.36,P=0.013).淋巴结转移的患者化疗前化疗后LMvD均高于淋巴结未转移者.结论 化疗前P-AKT的表达及化疗后AKT和P-AKT的表达与肿瘤微淋巴管生成呈正相关,LMvD与淋巴结的转移呈正相关,化疗前P-AKT的表达有可能作为预测宫颈癌新辅助化疗疗效的指标.

Expression of AKT,P-AKT in cervical cancer before and after neoadjuvant chemotherapy and its effect on lymphangiogenesis and clinical significance

OBJECTIVE The therapeutic effect of neoadjuvant chemotherapy (NACT)in cervical cancer has been controversial.The PI3K/AKT pathway plays an important role in tumor cell proliferation,migration and invasion and an-ti-apoptosis.The aims of this article was to examine the effect of AKT and P-AKT on lymphangiogenesis in cervical squa-mous carcinoma with neoadjuvant chemotherapy and analyze the association of their expression with the clinical efficacy. METHODS The expression of AKT,P-AKT and density of lymphatic microvessels (LMvD)in 47 cervical squamous cell carcinomas treated with neoadjuvant chemotherapy from March 1,2011 to March 31,2016 in Binzhou Medical College,Af-filiated Hospital were detected by immunohistochemistry method.RESULTS The expression of AKT and P-AKT before chemotherapy was detected in 93.6% and 72.3% of all cases,while the expression of AKT and P-AKT after chemothera-py was observed in 44.7% and 36.2%.The expression of AKT in tumors after neoadjuvant chemotherapy was different with that in tuomrs before and after neoadjuvant chemotherapy (P <0.001).LMvD count was 20.87±3.31 in cervical squamous cell carcinoma before chemotherapy and 16.47±3.44 after chemotherapy.The level of LMvD after chemother-apy was decreased (t=6.32,P <0.001).The positive rate of AKT positive in cervical squamous cell carcinoma was 21.14 ±3.19,which was higher than that in negative group (17.00±3.00).Spearman correlation analysis showed that LMvD was positively correlated with P-AKT expression before and after chemotherapy (rs = 0.39;P = 0.007,rs = 0.66,P <0.001).LMvD was positively correlated with AKT expression after chemotherapy (rs =0.58,P <0.001).There was a positive correlation between lymph node metastasis and LMvD before and after chemotherapy (rs =0.44,P <0.001;rs =0.36,P =0.013).Whether before chemotherapy or after chemotherapy,LMDv in lymph node-positive patients was higher than that in lymph node-negative patients.CONCLUSIONS The expression of P-AKT before neoadjuvant chemo-therapy and the expression of AKT and P-AKT after neoadjuvant chemotherapy are positively correlated with the lym-phangiogenesis,and LMvD is positively correlated with the lymph node metastasis.Before chemotherapy,P-AKT expres-sion may be served as a potential predictor of neoadjuvant chemotherapy for cervical cancer.