缺氧诱导因子1、血管内皮生长因子和环氧化酶-2在乳腺癌中表达的意义
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摘要
目的研究缺氧诱导因子1(HIF-1α)、血管内皮生长因子(VEGF)、环氧化酶-2(COX-2)在乳腺癌中的表达与发生、发展及侵袭转移的关系。方法应用免疫组织化学S-P法检测61例乳腺癌前病变患者[25例导管非典型增生(ADH)、36例导管原位癌(DCIS)]和78例乳腺浸润性癌患者(IDC)组织中HIF-1α、VEGF和COX-2的表达情况,并与52例乳腺增生患者标本作为对照。采用SPSS 17.0软件包,HIF-1α,VEGF和COX-2样本阳性率组间比较采用χ~2检验。结果(1)HIF-1α、VEGF和COX-2在乳腺IDC中的阳性表达率分别为67.9%、64.1%和79.5%,明显高于在乳腺癌前病变(DCIS为44.4%、44.4%、55.6%;ADH为28.0%、32.0%、36.0%)和乳腺普通导管增生病变(7.7%,23.1%,15.4%)中的表达,差异有统计学意义(χ~2=5.696,12.424,28.415;P<0.05);(2)乳腺癌前病变中DCIS与ADH比较,HIF-1α(χ~2=1.699,P>0.05)、VEGF(χ~2=0.957,P>0.05)、COX-2(χ~2=2.263,P>0.05),差异无统计学意义;(3)HIF-1α、VEGF和COX-2在乳腺IDC中高表达与患者年龄(χ~2=3.410,0.509,0.103;P>0.05)、肿瘤大小(χ~2=2.010,0.143,0.304;P>0.05)无关,而与组织学分级(χ~2=16.268,15.695,11.272;P<0.05))和淋巴转移(χ~2=6.321,13.020,19.123;P<0.05)相关;(4)HIF-1α、VEGF和COX-2三者在乳腺癌中的表达呈正相关(r=0.263,χ~2=5.412,P<0.05;r=0.436,χ~2=9.441,P<0.05)。结论 HIF-1α、VEGF和COX-2高表达是乳腺癌发生、侵袭转移行为的重要生物学标志,HIF-1α可能发生在癌变早期阶段,是乳腺癌的早起事件;VEGF和COX-2与乳腺癌进展期侵袭转移更相关;HIF-1α、VEGF和COX-2联合检测可作为判断乳腺癌预后的指标。
Objective To investigate the expression of HIF-1α,VEGF and COX-2 in breast carcinoma and their associations with the occurrence,development,invasion and metastasis of breast carcinoma.Methods The expression of HIF-1α,VEGF and COX-2 was detected by immunohistochemistry S-P method in sixty-one cases of precancerous lesions including twenty-five cases of atypical ductal hyperplasia( ADH),thirty-six cases of ductal carcinoma in situ( DCIS),and seventy-eight cases of invasive ductal carcinoma( IDC) of the breast. Twenty-six cases of hyperplasia breast tissues were selected as control group. The differences of positive rates of HIF-1α,VEGF and COX-2 were compared with chi-square test. Results The positive rates of HIF-1α,VEGF and COX-2 in IDC were 67. 9%,64. 1% and 79. 5% respectively; the positive rates in DCIS were 44. 4%,44. 4%,55. 6% respectively,and the positive rates in ADH were28. 0%,32. 0%,36. 0% respectively,which were higher than those in hyperplasia breast tissues( 7. 7%,23. 1%,15. 4%,χ~2= 5. 696,12. 424,28. 415; P < 0. 05). However,there were no significant differences in the positive expression rates of HIF-1α,VEGF and COX-2 between ADH and DCIS tissue( χ~2= 1. 699,0. 957,2. 263; P > 0. 05). There was a correlation between over-expression of HIF-1α,VEGF and COX-2 with the histological grade and lymph node metastasis of IDC repectively,wherease without correlation with age and size of tumor( χ~2= 3. 410,0. 509,0. 103; P > 0. 05). The expression of COX-2 was positively correlated with HIF-1α and VEGF( r =0. 263,χ~2= 5. 412,P < 0. 05; r = 0. 436,χ~2= 9. 441,P < 0. 05).Conclusions The overexpression of HIF-1α,VEGF and COX-2 might be important biological markers for the invasion,lymph node metastasis and distant metastasis of IDC. The combined detection of HIF-1α,VEGF and COX-2 is a predictor for prognosis.
Objective To investigate the expression of HIF-1α,VEGF and COX-2 in breast carcinoma and their associations with the occurrence,development,invasion and metastasis of breast carcinoma.Methods The expression of HIF-1α,VEGF and COX-2 was detected by immunohistochemistry S-P method in sixty-one cases of precancerous lesions including twenty-five cases of atypical ductal hyperplasia( ADH),thirty-six cases of ductal carcinoma in situ( DCIS),and seventy-eight cases of invasive ductal carcinoma( IDC) of the breast. Twenty-six cases of hyperplasia breast tissues were selected as control group. The differences of positive rates of HIF-1α,VEGF and COX-2 were compared with chi-square test. Results The positive rates of HIF-1α,VEGF and COX-2 in IDC were 67. 9%,64. 1% and 79. 5% respectively; the positive rates in DCIS were 44. 4%,44. 4%,55. 6% respectively,and the positive rates in ADH were28. 0%,32. 0%,36. 0% respectively,which were higher than those in hyperplasia breast tissues( 7. 7%,23. 1%,15. 4%,χ~2= 5. 696,12. 424,28. 415; P < 0. 05). However,there were no significant differences in the positive expression rates of HIF-1α,VEGF and COX-2 between ADH and DCIS tissue( χ~2= 1. 699,0. 957,2. 263; P > 0. 05). There was a correlation between over-expression of HIF-1α,VEGF and COX-2 with the histological grade and lymph node metastasis of IDC repectively,wherease without correlation with age and size of tumor( χ~2= 3. 410,0. 509,0. 103; P > 0. 05). The expression of COX-2 was positively correlated with HIF-1α and VEGF( r =0. 263,χ~2= 5. 412,P < 0. 05; r = 0. 436,χ~2= 9. 441,P < 0. 05).Conclusions The overexpression of HIF-1α,VEGF and COX-2 might be important biological markers for the invasion,lymph node metastasis and distant metastasis of IDC. The combined detection of HIF-1α,VEGF and COX-2 is a predictor for prognosis.
引文
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[10]Peng ZH,Wan DS,Li LR,et al.Expression of COX-2,MMP-2 and VEGF in stageⅡandⅢcolorectal cancer and the clinical significance[J].Hepatogastroenterology,2011,58(106):369-376.
[2]Sakthivel KM,Guruvayoorappan C.Acacia ferruginea inhibits tumor progression by regulating inflammatory mediators-(TNF-a,i NOS,COX-2,IL-1β,IL-6,IFN-γ,IL-2,GM-CSF)and pro-angiogenic growth factor-VEGF[J].Asian Pac J Cancer Prev,2013,14(6):3909-3919.
[3]阮玉凤,孙璟,吴方,等.COX-2基因多态性与结直肠癌发病风险的关系研究[J].国际消化病杂志,2013,33(4):260-263,272.
[4]王刚平,张红,张作峰,等.乳腺导管内增生性病变合并浸润性导管癌的临床病理分析[J].中德临床肿瘤学杂志(英文版),2013,12(12):574-580.
[5]王刚平,梁云爱,张作峰,等.CD105标记微血管密度及HIF-1α在乳腺癌及癌前病变中的表达及意义[J/CD].中华临床医师杂志(电子版),2013,7(16):7386-7391.
[6]王洪远,王刚平,王绍田,等.COX-2、TGF-β1和HIF-1α表达与乳腺癌侵袭转移的关系[J].临床肿瘤学杂志,2008,13(5):417-420.
[7]翟俊山,李楠,王卉,等.环氧化酶-2在胃癌组织中的表达及与患者预后的关系[J].中华消化内镜杂志,2007,24(5):379-381.
[8]Yun'ai Liang,Zengxin Li,Gangping Wang.Expression of HIF-1αin breast cancer and precancerous lesions and the relationship to clinicopathological features[J].Chinses-German J Clin Oncol,2014,13(1):23-28.
[9]王刚平,张红,梁云爱,等.β-tubulin-Ⅲ、E-cadherin和α-catenin在乳腺癌及癌前病变中的表达及意义[J/CD].中华诊断学电子杂志,2013,1(1):57-61.
[10]Peng ZH,Wan DS,Li LR,et al.Expression of COX-2,MMP-2 and VEGF in stageⅡandⅢcolorectal cancer and the clinical significance[J].Hepatogastroenterology,2011,58(106):369-376.