| Objective:To detect the protein expression of epidermal growth factor receptor(EGFR), differentiated embryo-chondrocyte expressed gene1, differentiated embryo-chondrocyte expressed gene2, hypoxia inducible factor1α(HIF1α), signal transducer and activator of transcripton3(STAT3) and vascular endothelia growth factor(VEGF) in lung adenocarcinoma and investigate the relationship between the expression and clinicopathological characteristics and the correlation exist among them.Methods To examine the75specimens from primary lung adenocarcinoma patient’s.Their ages ranged from37to84years (median61years),41male and34female. There were20cases which the tumor size were more than3cm, less than3cm55.There were35patients did not involve in lymph node metastasis and40involved in. Distance metastasis was present in5/75patients. Nine patients had TNM1and46TNM2and20TNM3-4. Among75patients there were38cases in low differenced stage,33median,4high.Immunohistochemistry was used to detect the expression of EGFR, DEC1, DEC2, HIFla, STAT3and VEGF. The different score criteria were applied according to different protein moleculars.The statistical analysis between different variables was done using the Chi-Square test and Fisher’s exact test with SPSS11.5.Results:l.The expression of EGFR、DEC1、DEC2、HIF1α、STAT3and VEGF and the association with clinicopathological characteristics.(1)The expression of EGFR was mainly in the cell cytoplasm and on the membrane, while the intensity and positive staining distribution of each sample were different. In adjacent normal lung tissues,the expression of EGFR in the cytoplasm was62.67%(47/75), on the membrane2.67%(2/75). In contrast, the higher levels of EGFR expression were revealed in cytoplasm was80.00%(60/75) and on membrane45.33%(34/75) in adenocarcinoma tissues. There was statistically difference of EGFR expression in the cytoplasm(χ2=5.51,p=0.02) and on cell membrane (χ2=37.43,p=0.00) in two kinds of tissues.(2) The expression of DEC1mainly in the cytoplasm and nucleus, while rarely on the cell membrane. The expression of DEC1in the cytoplasm and nucleus was100.00%(75/75)and2.67%(2/75) respectively in adjacent normal lung tissues. At the same time, the levels of DEC1expression was revealed in the cytoplasm98.67%(74/75)and in the nucleus54.67%(41/75)in malignant neuplastic tissues. There was no significant difference of DEC1cytoplasm expression (χ2=1.01,p=0.50) in two kinds of tissues, while there was statistically difference in the nucleus (χ2=40.64,p=0.00).(3) The expression of DEC2was mainly in the cytoplasm, while rarely in the nucleus, no expression was found on the membrane. In adjacent and cancer tissues, the expression of DEC2in the cytoplasm were both98.67%(74/75),there were no statistics difference (χ2=0,p=0.75).The nuclear DEC2expression in neoplastic tissue was20.00%(15/75),statistically higher than that of adjacent tissues (χ2=13.71,p=0.00).(4)The cytoplasic expression of HIF1α was predominant compared to cell nuclear expression. The expression of HIF1α was66.67%(50/75) in neoplatic tissues, significantly higher than that of adjacent tissues(10.7%,8/75)(χ2=48.88,p=0.00).(5)The expression of STAT3was mainly in the cytoplasm and nucleus. The cytoplasm expression of STAT3was9.33%(7/75) in adjacent tissues, which significantly lower than65.33%(49/75))in cancer tissues. At the same time, no HIFla nuclear expression revealed in adjacent tissues and in adenocarcinoma tissues was22.7%(17/75). There was significant difference of STAT3nuclear expression in two kinds of tissues.(6)The expression of VEGF was only showed in the cytoplasm, no expression was found in cell nucleus and on the membrane. The expression in cancer tissues was86.67%(65/75) significantly higher than16.00%(12/75) in adjacent tissus (χ2=75.00,p=0.00).(7) Except tumor tissue differentiation (χ2=6.81,p=0.033) and lymph node metastasis (χ2=7.44,p=0.006),EGFR expression was not correlated with gender, age,large tumor size,T stage and distance metastasis.(8) Except age (χ2=4.72,p=0.026) and large tumor size (χ1=3.71,p=0.047),DEC1nuclear expression was not correlated with gender, tumor tissue differentiation, TNM stage, lymph node metastasis and distance metastasis.(9) No relationship was found between the DEC2nuclear expression and clinicopathological characterisics. In positive patients, there were less specimens which tumor size was larger than3cm(χ2=3.241,p=0.07).(10)HIF1α expression was correlated with distance metastasis (χ1=14.6,p=0.00) and TNM stage(χ2=7.07,p=0.03), no association was found between HIF1α expression and other characteristics.(11)Nuclear expression of STAT3was correlated with tumor size and TNM stage,while cytoplasm expression did not find the association with clinical characteristics.(12)VEGF expression related with gender(χ2=5.60,p=0.02) and distance metastasis (χ2=10.10,p=0.02).Compared to histologic differentiation, the statistics value was on the margin.(χ2=5.72,p=0.06)2. The correlation exist between EGFR,DEC1,DEC2,HIF1α,STAT3and VEGF.(1) In patients with lymph node metastasis, the positive percentage were EGFR-/DEC1+33.00%, EGFR-/DEC1-45.00%, EGFR+/DEC1-57.00%, EGFR+/DEC1+80.00%,respetively. There was a statistically significant difference between EGFR+/DEC1+and EGFR-/DEC1-(χ2=5.23,p=0.02), at the same time, there was a statistically significant difference between EGFR+/DEC1+and EGFR-/DEC1+(χ2=9.06,p=0.03), while no statistical difference between EGFR+/DEC1+and EGFR+/DEC1-(χ2=2.07,p=0.14).(2)The nuclear expression of DECland DEC2had association with each other (χ2=6.97,p=0.01). There were16cases expressed DEC2, in which14cases had DEC1activity;In31cases no DEC1expressed,only2cases DEC2expressed positive; In59cases negative DEC2expression,29cases negatively and30cases positively expressed DEC1.(3) Related to the tumors size,the pattern of DEC1-/DEC2+(χ2=2.31,p=0.12) and DEC1+/DEC2+(χ2=1.78,p=0.30) both had no statistical difference.The pattern of DEC1-/DEC2-and DEC1+/DEC2+had statistical differences (χ2=5.04,p=0.03), the latter had much more samples which were larger than3cm,24cases vs.7cases.(4) DEC1-/DEC2-pattern had more stage TNM2patients (21casesvs.5case), DEC1+/DEC1+had more stage TNM1patients, which had statistical difference (χ2=6.48,p=0.04).(5)EGFR membrane expression was correlated with HIF1α (χ2=4.55,p=0.03); the statistical value between EGFR membrane expression and VEGF expression was on margin(χ2=2.99,p=0.08).(6)Except DEC2nuclear expression(χ2=2.42,p=0.11), HIF1α was statistically associated with EGFR membrane expression(χ2=4.55,p=0.03), DEC1nuclear expression,STAT3cytoplasm and nucleus expression (χ2=10.63,p=0.001;χ2=7.45,p=0.004). The statistical value between HIF1α and VEGF was on the margin(χ2=3.69,p=0.06).(7)The nuclear localization of STAT3expression had significantly difference of cytoplasm expression(χ2=11.66,p=0.00). The STAT3expression in nucleus was correlated to DEC1(χ2=12.96,p=0.00), DEC2(χ2=10.06, p=0.004) and HIF1α expression (χ2=7.45, p=0.004). The STAT3expression in cytoplasm was only correlated to DEC1(χ2=4.97,p=0.02) and HIF1α (χ2=10.63,p=0.001)Conclusions:(1) EGFR、DEC1、DEC2、STAT3and VEGF protein was detected together for the first time in lung adecarcinoma,and all highly expressed in cancer tissue.(2) EGFR and DEC1protein promotes lymph node metastasis in lung adenocarcinoma.(3) The co-expression of DEC1and DEC2repressed tumor growth and decrease the size of tumor.(4) HIF1α maybe lied at the center site of the adaption to hypoxia regulation of EGFR、DEC1、STAT3and VEGF.(5)Transcription factor of DEC1、DEC2and HIFla were highly related to STAT3respectively; The nuclear STAT3expression may have different function compared to cytoplasm STAT3expression in lung adenocarcinoma. |
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