The Relationship Between The Expression Of Hypoxia Marker CA IX And Drug Resistance, Invasion And Migration In Breast Cancer

Part I The Influence of CAIX to the Effect of Neoadjuvant Chemotherapy in Breast CancerPurpose1. Through the observation of the expression of CA IX before and after neoadjuvant chemotherapy in breast cancer, evaluate the value of it as the reference for the individual chemotherapy for breast cancer.2. Through the observation of the expression changes of CA IX before and after neoadjuvant chemotherapy with P-gp substrate drug regimen, explore whether the tumor hypoxic microenvironment is relevant to the function of P-gp drug pump in multidrug resistance.Methods Select local advanced breast cancer cases in Huashan Hospital, Fudan University from June2009to November2012, ultrasound-guided Mammotome vacuum-assisted biopsy system puncture a tumor biopsy, which was diagnosed an invasive ductal carcinoma. Patients received4courses of CET neoadjuvant chemotherapy and subsequently underwent modified radical mastectomy. The original biopsy specimens of patients and postoperative residual tumor foci paraffin sections detected the expression of CA IX, P-gp by immunohistochemistry. Assessed in accordance with JBSC standard neoadjuvant chemotherapy, the patients were divided into chemotherapy does not answer, chemotherapy, partial response, and chemotherapy complete response group, CA Ⅸ expression in each group were compared to determine the influence of tumor hypoxic microenvironment on the effect of breast cancer chemotherapy; according to the patient biopsies expression of P-gp grouping, to compare the two sets of CA IX expression, to explore whether the tumor hypoxic microenvironment multidrug resistance is relevant to the P-gp pathway. Results A total of98patients were enrolled in the study, the expression of CA IX is related to neoadjuvant chemotherapy. CA IX expression after neoadjuvant chemotherapy in patients is higher than that before chemotherapy, it has a statistically significant difference (P<0.0001*); CA IX expression of chemotherapy partial response and chemotherapy complete response group was significantly higher than non-response group (P=0.006*) before chemotherapy; the change of CA IX expression before and after neoadjuvant chemotherapy in the non-response group is much higher than that in the partial response group, with a statistically significant difference (P=0.0188*). CA IX expression between the two groups before and after neoadjuvant chemotherapy doesn’t have a statistically difference according to whether the expression of P-gp packet.Conclusions Chemotherapy increased tumor hypoxia. There’s a Potential correlation between tumor hypoxia microenvironment and breast cancer chemotherapy drug enhanced. The expression of hypoxia marker CA IX in breast cancer is related to the effect of neoadjuvant chemotherapy and it can provide a reference to the adjuvant chemotherapy program for individual patient. Tumor hypoxia microenvironment has no relationship with the function of P-gp drug pump in multidrug resistance. It may be involved in the process of multidrug resistance by intracellular pH adjustment path.Part II The Relationship between CA IX Expression and Breast Cancer Tumor Proliferation, Molecular Subtyping and Prognosis of PatientsPurpose To investigate the relationship between EGFR expression and multidrug resistance in human breast cancer cells and the underlying mechanisms.Methods The research objection is the same to the previous part. Biopsy specimens of patients and primary tumor of postoperative residual tumor detected the expression of CA IX and human epidermal growth factor receptor2(HER-2) by immunohistochemistry. Patients with biopsy specimens from Huashan Hospital, Fudan University, pathological department do the Immunohistochemical detection of estrogen receptor (ER), progesterone receptor (PR), Ki-67and other molecular biology markers. Through enhanced MRI assess the tumor size before and after neoadjuvant chemotherapy. The specimens after modified radical surgical were evaluated routinely by the Department of Pathology with tissue type, histological grade, lymph node metastasis. Patients diagnosed as breast cancer for three years for survival follow-up by telephone follow-up or home follow-up. Last follow-up time was the March18,2013.Results The expression of hypoxia markers CA IX has a correlation with HER-2(P=0.0003*). But CA IX were not correlated with either the expression of tumor proliferation marker Ki-67or breast cancer molecular subtyping. CA IX expression has no correlation with the tumor size before and after neoadjuvant chemotherapy, lymph node metastasis. Higher CA IX expression before neoadjuvant chemotherapy is relative to poor prognosis, but no statistically significant differences.Conclusions Tumor hypoxic microenvironment has a correlation with HER-2expression in breast cancer, While it has no relationship with breast cancer molecular subtyping or the ability of tumor proliferation. CA IX expression as a breast cancer prognostic factor remains problematic.