Study Of Expression And Correlation Of COX-2, MMP-2 And Ki-67 In Neoadjuvant Chemotherapy Of Breast Cancer

Objective: To explore the expression of COX-2, MMP-2 and Ki-67 in neoadjuvant chemotherapy of breast cancer, and the correlation of COX-2, MMP-2 and Ki-67.Methods: The expression of COX-2, MMP-2 and Ki-67 in 48 samples formalin-fixed paraffin-embedded primary breast cancer received neoadjuvant chemotherapy in our hospital from January 2005 to March 2007 was examined by immunohistochemical staining with Rabbit anti-Cox-2 monoclonal antibody, Rabbit anti-MMP-2 multiclonal antibody and Mouse anti-Ki-67 monoclonal antibody respectively.Results: Among the 48 evaluable patients,6(12.5%) showed complete remission , 28 (58.3%) showed partial remission, 12 (25.0%) showed stable disease and 2(4.2%) showed disease progression. The overall response rate to neoadjuvant chemotherapy(NACT) was 70.8%. The effect of NACT had a significantly negative correlation with COX-2 expression and a significantly positive correlation with Ki-67 expression(P<0.05), but had no correlation with MMP-2 expression(P>0.05). The expression of COX-2 and Ki-67 in post-neoadjuvant chemotherapy [41.7% and (33.23±18.11)%] was significantly lower than that in pro-neoadjuvant chemotherapy [62.5% and (46.81±23.17)%](P<0.05), the positive rate of MMP-2 had no significant change(P>0.05), but after chemotherapy the change of expression intensity of MMP-2 had statistic significance(P<0.05). Before chemotherapy, COX-2 expression intensity was correlated with MMP-2(r=0.439, P<0.01). After chemotherapy, COX-2 expression intensity was correlated with MMP-2(r=0.450, P<0.01). Before neoadjuvant chemotherapy, the Ki-67 index was (56.07±17.37)% in COX-2 positive group while it was (27.32±16.28)% in the negative group, the Ki-67 index was (51.92±22.55)% in MMP-2 positive group while it was (27.40±13.57)% in the negative group. After neoadjuvant chemotherapy, the Ki-67 index was (44.65±17.38)% in COX-2 positive group while it was (25.07±13.88)% in the negative group, the Ki-67 index was (38.81±19.39)% in MMP-2 positive group while it was (23.06±9.39)% in the negative group. COX-2 and MMP-2 had positive correlation with Ki-67 before and after neoadjuvant chemotherapy(P<0.01).Conclusions: The expression of COX-2 and Ki-67 as molecular markers could guide chemotherapy and predict its response in breast cancer, but MMP-2 had no correlation with chemotheapy response. NACT could significantly change COX-2 expression in breast cancer to supress tumor progression. NACT had less effect on the postive rate of MMP-2, but may change MMP-2 expression intensity to depress tumor invasiveness. NACT could significantly slow down Ki-67 index, inhibit tumor cell proliferation. NACT could supress tumor progression, reduce the invasion and metastasis of breast cancer through the pathway of supress COX-2 expression, down regulation the expression of MMP-2 and inhibit tumor cell proliferation.