血清血管内皮生长因子C水平及癌组织中环氧化酶2的表达与乳腺癌淋巴道转移的关系

目的 探讨乳腺癌患者术前血清血管内皮生长因子C(sVEGF-C)水平、组织中环氧化酶2(COX-2)表达与乳腺癌淋巴道转移的关系.方法 采用ELISA法检测68例乳腺癌患者、35例乳腺良性病术前以及12名健康女性sVEGF-C水平.免疫组化SP法检测相应乳腺癌患者组织标本中COX-2表达及淋巴管密度(LMVD);分析sVEGF-C、COX-2及LMVD表达之间的关系.结果 (1)乳腺癌患者术前sVEGF-C水平(49±8)pg/ml显著高于健康女性志愿者(5±3)pg/ml和乳腺良性疾病者(8±4)pg/ml;(2)乳腺癌组织COX-2阳性表达率(44.1%)显著高于乳腺良性疾病(11.4%)(P=0.002);LMVD主要位于癌旁组织,癌巢中少有表达;癌旁组织中LMVD(8.7±4.7)较乳腺良性疾病组织中表达(1.8±1.7)显著增多(P=0.002);(3)在乳腺癌患者sVEGF-C水平增高者中,不但COX-2的表达显著高于sVEGF-C水平正常者COX-2的表达(P=0.024),而且LMVD(8.7±3.9)也显著高于sVEGF-C正常者的LMVD(5.6±3.3)(P=0.039);(4)乳腺癌患者COX-2表达阳性组LMVD(9.5±3.7)明显高于COX-2表达阴性组LMVD(6.0±3.8)(P=0.012);(5)在腋淋巴结转移阳性患者中,sVEGF-C水平、COX-2及LMVD表达均高于腋淋巴结转移阴性组(P值分别为0.025,0.022和0.002).结论 sVEGF-C、COX-2及LMVD在乳腺癌的淋巴道转移中有重要作用,可作为估计乳腺癌有无淋巴结转移的参考指标.

The relationship between lymphatic metastasis and serum vascular endothelial growth factor C and cyclooxygenase 2 expression in breast cancer

OBJECTIVE: To investigate the relationship among the serum vascular endothelial growth factor C (sVEGF-C), expression of cyclooxygenase 2 (COX-2), and lymph vessel density (LMVD), and to discuss their role in tumor progression and lymphatic metastasis. METHODS: sVEGF-C level was detected by ELISA in 68 pre-operation breast cancer patients, 35 breast benign disease patients, and 12 healthy women. Immunohistochemical method was used to detect the expression of COX-2 and lymphatic vessel endothelial hyaluronidase receptor (LYVE)-1 in the breast cancer tissues and benign disease tissues obtained during operation. RESULTS: (1) The sVEGF-C level of the pre-operation breast cancer group was (49 +/- 8) pg/ml, significantly higher than those of the begin tumor group (8 +/- 4) pg/ml, P = 0.045] and the healthy women (5 +/- 3) pg/ml, P = 0.003]. (2) The COX-2 overexpression positive rate in the breast cancer tissues was 44.1%, significantly higher than that in the begin disease tissues (11.4%, P = 0.002). Higher than that in the begin disease tissue; the LMVD overexpression in the breast cancer tissues was mainly located in the para-carcinoma tissue (8.7 +/- 4.7), significantly higher than that in the begin disease tissues (1.8 +/- 1.7, P = 0.002). (3) The COX-2 overexpression rate of the patients with a high sVEGF-C level was significantly higher than that of the patients with a low sVEGF-C level (P = 0.024). The LMVD level in the breast cancer of the sVEGF-C high level group was (8.7 +/- 3.9), significantly higher than that of the sVEGF-C normal group (5.6 +/- 3.3, P = 0.039). (4) The LMVD in the COX-2 overexpression breast cancer group was 9.5 +/- 3.7, significantly higher than that in the COX-2 negative group (6.0 +/- 3.8, P = 0.012). (5) The sVEGF-C level, COX-2, and LMVD expression in the breast cancer patients with lymphatic metastasis were significantly higher than those in the patients without lymphatic metastasis (P = 0.025, 0.022, and 0.002 respectively). CONCLUSION: VEGF-C, COX-2, and LMVD play important roles in the lymphatic metastasis of breast cancer. They may be important prognostic factors in evaluating breast cancer lymphatic metastasis.