Characteristics Of P-glycoprotein And Osteopontin During The Development Of Intrinsic Multidrug Resistance In Breast Carcinoma

Objective: Breast carcinoma is one of the most common malignant tumors of women, and chemotherapy is very important in its combined therapeutic strategy. Multidrug resistance (MDR), including acquired MDR and intrinsic MDR, often leads to the failure of chemotherapy in breast cancer. At present, there have been many studies for the acquired MDR, but few for the intrinsic MDR. In this study, the changes of multidrug resistance relative proteins were detected, and relationships between the expression of these proteins and some clinicopathological characteristics were surveyed in the patients with breast carcinoma. Studying the genesis mechanisms and influential factors of intrinsic MDR could be helpful to selecting chemotherapy regimen and improving therapeutic effects.Methods: Expression of P-glycoprotein (P-gp) and osteopontin (OPN) were detected by immunohistochemistry in 40 cases of breast carcinoma, consisting of 25 cases with neoadjuvant chemotherapy (NAC group) and 15 cases without neoadjuvant chemotherapy (non-NAC group); MDR1 mRNA and OPN mRNA were detected by RT-PCR. And the relationships between these proteins expression and the clinicopathological characteristics such as tumor staging, pathohistology category, hormone receptor status, C-erbB-2 and P53 protein condition, and NAC program were evaluated. The same indexes were detected in 10 cases of breast adenosis as the control group. Results: The positive rate of P-gp expression was 84.0% (21/25), 46.7 %(7/15) and 0 in NAC group, non-NAC group and control group, respectively. There were significant differences among the three groups (P<0.01).The positive rate of OPN protein expression was 76.0% (19/25), 73.3% (11/15) and 0 in NAC group, non-NAC group and control group, respectively. There was no significant difference between NAC group and non-NAC group (P >0.05).The positive rate of MDR1 mRNA expression was 84.0% (21/25), 53.3% (8/15) and 10% (1/10) in NAC group, non-NAC group and control group, respectively. There were significant differences among the three groups (P<0.01).The positive rate of OPN mRNA protein expression was 72.0% (18/25), 66.7% (10/15) and 0 in NAC group, non-NAC group and control group, respectively. There was no significant difference between NAC group and non-NAC group (P>0.05).Conclusions: Some tolerances to chemotherapeutics increase during the oncogenesis process of breast carcinoma. MDR1/P-gp and OPN is associated with the intrinsic MDR in breast carcinoma. The level of MDR1/P-gp also could be increased by chemotherapy, but the level of OPN couldn't. P-gp expression correlates directly to P53 protein status, and so dose OPN expression and tumor staging.