Expression And Significance Of C-erbB-2, NF-κB, VEGF-C And Its Receptor In Breast Cancer

Objective:To investigate the protein expression of nuclear transcription factor NF-κB ,VEGF-C and its receptor VEGFR-3 in breast cancers, and the relationship among NF-κB , VEGF-C ,VEGFR-3 and clinicopathologic parameters such as tumor size , histological grading, pathological grading and nodal status. To explore the expression level and significance of C-erbB-2 mRNA in breast cancers Methods:40 human breast cancer tissue samples and 10 non-carcinomatous tissues of adjacent tumor were collected, and protein expression of NF-κB P65, P50, VEGF-C, VEGFR-3, as while as C-erbB-2, ER, PR were measured by immunohistological PV two-step method . The relative expression level of C-erbB-2 mRNA in breast cancer tissue were detected by fluorescent quantitative reverse transcription PCR (FQ-RT-PCR). Results:1. The positive rate of NF-κB was 45% (18/40) .The positive rate of P65 and P50 were 32.5% (13/40) and 40.0% (16/40) respectively, their expression were well positive correlated (r=0.632, P<0.01), meaning that P65/P50 dimer is the important active complex of NF-κB in breast cancer. Moreover, NF-κB and C-erbB-2 protein were positive correlated (r=0.442, P=0.004 ) , meaning that NF-κB and C-erbB-2 protein play an important role in the occurrence and malignant transformation of breast cancer. However, NF-κB didn't correlate with ER or PR. The expression of NF-κB in Ⅲ graded group was stronger compared with Ⅰ or Ⅱ groups ( P= 0.018) . But NF-κB didn't related to tumor size , pathological grading and nodal status.2. The positive rate of VEGF-C and VEGFR-3 in breast cancer were 70.0 % (28/40) and 57.5 % (23/40) respectively, more higher than that in non-carcinomatous tissuesof adjacent tumor; moreover, their expression were well positive correlated (r=0.761). Both NF-kB and C-erbB-2 were correlated with VEGF-C (r value were 0.373 and 0.342 respectively).The positive rate of VEGF-C and VEGFR-3 were 90.0% and 82.4% respectively in lymph node metastasis group , significantly higher than that of no lymph node metastasis group ( 56.5% and 39.1% respectively). The number of VEGFR-3 positive vessels in lymph node metastasis group (8.54±2.54) was significantly higher than that of no lymph node metastasis group ( 4.73±2.46) . 3. The positive rate of C-erbB-2 protein and C-erbB-2 mRNA were 42.5 % (17/40) and 37.5 % (15/40) respectively, the status of C-erbB-2 protein in IHC test had the high concordance of the status of C-erbB-2 mRNA in RT-PCR (kappa=0.792, P <0.01) ,meaning that the amplification of C-erbB-2 oncogene in breast cancer induces increase accordingly in its transcription and translation ,and that the expression level of C-erbB-2 mRNA may represent that of C-erbB-2 protein for the majority of breast cancers. Like C-erbB-2 protein, C-erbB-2 mRNA was negatively correlated with ER (r=-0.514, PO.01) , but not PR. The expression of C-erbB-2 mRNA in III graded group was stronger compared with the other two groups (P=0.018) . C-erbB-2 mRNA didn't related to tumor size , pathological grading and nodal status. Conclusions:1. NF-kB were activated abnormally in part of breast cancers . Its expression was positively correlated with C-erbB-2; furthermore, it expressed stronger in histologically graded group III compared with groups I and II. NF-kB and C-erbB-2 protein may play an important role co-operatively in the occurrence and malignant transformation of breast cancer, hence NF-kB may be a hopeful therapeutic target for breast cancer (especially ER7C-erbB-2+) .The expression of P65 and P50 were well positive correlated, meaning that P65/P50 heterodimer is the important active complex of NF-kB in breast cancer.