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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 relationship between the expression of hypoxia inducible factor 1 (HIF-1α), vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) in breast cancer and their development, invasion and metastasis. Methods Immunohistochemical SP method was used to detect the expression of HIF in 61 cases of breast precancerous lesions (25 cases of ductal atypical hyperplasia (ADH), 36 cases of ductal carcinoma in situ (DCIS)] and 78 cases of breast invasive ductal carcinoma (IDC) -1α, VEGF and COX-2 expression, and with 52 cases of breast hyperplasia patients as a control. SPSS 17.0 software package was used to compare the positive rates of HIF-1α, VEGF and COX-2 between the two groups. Results (1) The positive rates of HIF-1α, VEGF and COX-2 in breast IDC were 67.9%, 64.1% and 79.5%, respectively, which were significantly higher than those in breast cancer (DCIS 44.4%, 44.4%, 55.6 %; ADH was 28.0%, 32.0%, 36.0%) and normal ductal hyperplasia (7.7%, 23.1%, 15.4%), the difference was statistically significant (χ ~ 2 = 5.696,12.424,28.415; P (2) The expression of COX-2 (χ ~ 2 = 0.957, P> 0.05) was significantly different between DCIS and ADH in breast precancerous lesions (χ ~ 2 = ~ 2 = 2.263, P> 0.05). (3) The expression of HIF-1α, VEGF and COX-2 in breast IDC was significantly correlated with the age of patients (χ ~ 2 = 3.410,0.509,0.103; ), Tumor size (χ ~ 2 = 2.010,0.143,0.304; P> 0.05) but not with histological grade (χ ~ 2 = 16.268,15.695,11.272; (4) There was a positive correlation between the expression of HIF-1α, VEGF and COX-2 in breast cancer (r = 0.263, χ ~ 2 = 5.412, P <0.05) = 0.436, χ ~ 2 = 9.441, P <0.05). Conclusions High expression of HIF-1α, VEGF and COX-2 is an important biological marker of breast cancer invasion and metastasis. HIF-1α may be an early stage of breast cancer. HIF-1α may be an early event in breast cancer. VEGF and COX- Cancer progression is more related to invasion and metastasis; HIF-1α, VEGF and COX-2 joint detection can be used as a marker to determine the prognosis of breast cancer.