| Objective: Breast cancer is the most commonly diagnosed cancer and the second-most common cause of cancer-related death in women worldwide, with an estimated 1.4 million new breast cancer cases every year. Despite the improvement in treatment, therapy resistance remains a major problem in the clinic. Endocrine therapy has become the most important treatment option for hormone-sensitive patients, which is approximately 70% of all breast tumour. Molecular subtyping of breast cancer has identified distinct subtypes of breast cancer. Cancers that express the oestrogen receptor(ER) are divided into two broad categories as luminal A and B types, largely depending on whether the tumour has low or high proliferation respectively. Currently, the most widely used antiestrogen is thetriphenylethylene Tamoxifen(TAM). TAM is known to induce a statistically significant improvement in the overall survival rate of breast cancer. Unfortunately, endocrine-resistant ER-positive disease represents up to one-quarter of all breast cancers. Understanding the mechanisms of resistance, and the identification of novel therapeutic targets is of vital importance if the prognosis of breast cancer is to be further improved. Recent studies have shown that amplification of FGFR1 is associated with early relapse, and poor survival, specifically in ER positive and/or low differented breast cancer. FGFR1 over-expression may be a major factor contributing to the endocrine resistance of these tumours. Ki67, also known as MKI67, a nuclear protein associated with cellular proliferation, is a well-established marker for evaluating the proliferation of tumor cell and predicting the outcomes of patients. The aim of this study was to investigate the expression of FGFR1 protein and Ki67 in luminal subtype breast cancer, analyze the relationship between FGFR1、Ki67 with the clinical-pathological features and the association between them and understand the role of FGFR1、Ki67 in the endocrine-resistant of luminal subtype breast cancer. Furthermore, analyzing the correlation of the expression of FGFR1 and ER、PR in order to find some reliable evidence for the prognosis and the targeted therapy in luminal subtype breast cancers.Methods: This study adopted S-P immunohistochemical techniques to detect the positive expression of FGFR1、Ki67 in 72 cases of luminal subtype breast cancer tissue. Pathological examinations were carried out by two pathologists at the Department of Pathology of Hebei General Hospital, which had complete clinical data from 2009-03-01 to 2010-12-30. The relationship between FGFR1 、 Ki67 with the clinical-pathological features and the endocrine resistant was investigated. The expression of FGFR1、Ki67 in different molecular subtypes of luminal breast cancer were tested. Follow-up was performed by hospital visiting, telephone or mail, and counted from the first day after surgery and ended by 2014-6-30 or lost, the date of death. According to the follow-up data, the relationship between the expression of FGFR1、Ki67 and endocrine resistance in luminal subtype breast cancer had been analyzed. Further analysis was also of done the correlation of luminal subtypes with the endocrine resistance. SPSS13.0 statistical software was adopted for statistical analysis. The count data was determined by χ2 test or Fisher’s Exact test. Spearman rank correlation was used to analyze the association between two variables. Kaplan-Meier method was performed to assess endocrine resistance, long-rank test was used to analysis differences in relapse rate. All statistical significance was set at the 0.05 level of significance. Test levelα= 0.05.Results:1 In 72 luminal subtype breast cancer tissues, the total expression rate of FGFR1 in luminal subtype breast cancer was 34.72%(25/72). Among them, the expression in luminal B cases was 41.51%(22/53), which was significantly higher than that in luminal A cases 15.8%(3/19)(P<0.05). The expression rate of Ki67 was 70.83%(51/72).2 The expression of FGFR1 in luminal subtype breast cancer was associated with tumor size, lymph node metastasis and tumor grade(P<0.05). The expression of FGFR1 in tumor size>2cm was significantly higher than tumor size≤2cm group(P<0.05). In comparision with lymph node negative, the expression of FGFR1 was statistically higher in the lymph node metastasis(P<0.05). In the Ⅲ stage group, the expression of FGFR1 was significantly higher thanⅠ~Ⅱstage(P<0.05). And no significance difference was found between age, menstrual status or TNM stage(P>0.05). Patients with lymph node metastasis had a higher tendency to express Ki67(P<0.05) and there was no significance difference between age, menstrual status, tumor size or tumor grade(P>0.05).3 In 72 luminal subtype breast cancer, the expression of FGFR1 was positively correlated with that of Ki67 in luminal subtype breast cancer(rs=0.275, P=0.019).4 In 72 luminal subtype breast cancer, there were 37 cases of patients with endocrine resistance, the resistance rate was 51.39%(37/72). The positive expression of FGFR1 was 25 cases in which there were 18 cases occured resistant, and the resistant rate was 72%(18/25); Meanwhile there were 19 cases revealed resistant in the negative expression group and the resistance rate was 40.43%(19/47). Log-rank test showed that there was closely related to the expression of FGFR1 in the endocrine resistance of luminal subtype breast cancer.5 In 72 luminal subtype breast cancer, Ki67 status was divided into four groups, the resistance rate of the patients was 38.10%(8/21)、55%(22/40)、75%(6/8) and 33.33%(1/3) respectively(P>0.05).6 In 19 cases luminal A patients, endocrine resistance cases or death was 6 cases, the resistance rate was 31.58%(6/19). While the resistance rate in luminal B patients was 58.49%(31/53). Log-rank test showed there was significance in luminal subtype(P<0.05).7 The positive expression of FGFR1 and ER were 24 cases and the Spearman rank correlation revealed that there was no relationship between the expression of FGFR1 and ER(r=0.05, P=0.679). On the contrary, the data revealed that the expression of FGFR1 associated significantly with the positive expression of PR(r=-0.253, P=0.032).Conclusion:1 The expression in luminal B cases was significantly higher than luminal A cases. The expression of FGFR1 in luminal subtype breast cancer was associated with tumor size, lymph node metastasis and tumor grade.2 Patients with lymph node metastasis had a higher tendency to express Ki67, and no significance difference was found between age, menstrual status, tumor size, tumor grade or TNM stage.3 The expression of FGFR1 was positively correlated with that of Ki67 in luminal subtype breast cancer and there was no relationship between the expression of FGFR1 and ER. On the contrary, the data revealed a negative relation between the expression of FGFR1 and PR.4 FGFR1 positive expression had significance with endocrine resistance and luminal B breast cancers were more likely to develop resistance to endocrine, On the contrary, no significance difference was found between the expression of Ki67 and endocrine resistance. |
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