| Objective:The breast cancer is the most common malignant tumors of women among the world.According to the statistics,breast cancer ranks first among women in 140 countries around the world.Endocrine therapy is a very important treatment option for hormone-sentitive patients in China,which occupy approximately 60-70%of all breast cancer.However,clinical data show the primary or secondary resistance will occur in part of patients,leading to cancer progression or recurrence.Hypoxia inducible factor HIF-1?is the core factor of hypoxia response.Studies have shown that the increase of HIF-1?is related to the enhancement of local infiltration and metastasis energy of tumors and the insensitivity to radiotherapy and chemotherapy.HIF-1?may be one of the key regulators inducing endocrine resistance.Overexpression of Ki67,an antigen marking cell proliferation,suggests that cancer cells proliferate actively and have a poor prognosis.Studies have shown that Ki67 has important prognostic value in the diagnosis,treatment and prognosis of tumors.This study is aim to 1.Detect the expression of HIF-1?and Ki67 in 106 Luminal breast cancer specimens.2.Analyze the difference between the positive expression of HIF-1?and Ki67 in different pathological features.3.Discuss the relationship between the expression of HIF-1?and Ki67 with endocrine resistance.Methods:Immunohistochemical S-P method was used to detect the expression of HIF-1?and Ki67 in the surgical specimens of 106 unilateral breast cancer treated in mammary Surgery Department of Ningbo Women's and Children's Hospital from January 1,2013 to April 30,2014.Pathology was confirmed by two or more pathologists with high associate titles and hormone receptors are positive.Clinicopathological data and follow-up data were complete.Patients received standard endocrine therapy.SPSS 21.0 statistical software was used for data analysis,?~2 test or Fisher's exact test were used for data counting.Spearman correlation analysis was used for correlation between the two variables and Kaplan-Meier method was applied to evaluate the recurrence rate of endocrine resistance.Logrank test was used to evaluate the difference in relapse rate,and the differences are taken as having statistical significance when P<0.05..The test level is P=0.05.Results:1.Positive expression of HIF-1?and Ki67 proteins in Luminal breast cancer subtypes The positive rate of HIF-1?in breast cancer samples studied was 59.43%(63/106),the positive rate of Ki67 was 70.75%(75/106).The positive expression rate of HIF-1?in Luminal A was 33.33%(10/33),which was significantly lower than that in Luminal B 69.74%(53/76)(P<0.05).2.Relationship between HIF-1?and Ki67 proteins and clinicopathological features of Luminal breast cancer The expression of HIF-1?protein was correlated with tumor size,lymph node metastasis and histological grade of Luminal breast cancer(P<0.05).The expression of Ki67 in positive lymph node metastasis group was significantly higher than that in negative lymph node metastasis group(P<0.05).The expression in grade III was higher than that in grade I-II(P<0.05).3.There was a significant positive correlation between the expression of HIF-1?and Ki67 in Luminal breast cancer(rs=0.223,P=0.018).3.36 of the 106 patients were resistant to endocrine therapy.The total drug resistance rate was33.96%(36/106).In the HIF-1?positive group,27 cases were resistant,the drug resistance rate was 42.86%(27/63);The drug resistance rate was 20.93%(9/43)in the negative group.The drug resistance rate of Ki67 negative expression group was 16.1%(5/31);The drug resistance rate of Ki67 positive expression group was 41.3%(31/75).Significant difference was found between the expression of HIF-1?and Ki67 and endocrine resistance by Logrank method(P<0.05).4.In 30 cases of Luminal A breast cancer,4 cases had endocrine resistance leading to recurrence or metastasis,the drug resistance rate was 13.3%(3/40).Among 76 patients with Luminal B type,32 had drug resistance,the drug resistance rate was 42.1%(32/76).Significant difference was found in the rate of endocrine resistance among Luminal subtypes detected by Log rank method(P<0.05).Conclusion:1.Patients with Luminal B breast cancer are more likely to develop endocrine resistance than those with Luminal A.2.The expression of HIF-1?and Ki67 protein in Luminal B breast cancer was higher than that in Luminal A breast cancer.The expression of HIF-1?protein is related to the size of primary tumors,lymph node metastasis and histological grade of Luminal breast cancer patients.The positive rate of HIF-1?protein expression is relatively high in breast cancer tissues with large tumors,positive lymph node metastasis and high histological grade.The expression of Ki67 in patients with lymph node metastasis and higher histological grade was significantly higher than that in patients with negative lymph node metastasis.There was no significant difference between Ki67 and Luminal breast cancer in age,menstrual status,tumor size and clinical stage.3.There was a positive correlation between HIF-1?and Ki67 protein expression in Luminal breast cancer tissues,also there was a significant negative correlation between HIF-1?and PR in protein expression.4.The recurrence rate of HIF-1?and Ki67 positive patients after endocrine therapy was higher than that of negative patients,suggesting that the positive expression of HIF-1?and Ki67 is related to drug resistance in endocrine therapy. |
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