Expression Of FGFR1, VEGF And Their Correlation In Triple Negative Breast Carcinoma

Objective: Breast cancer is the most common malignant cancer in women worldwide, with an estimated 1.4 million new breast cancer cases. Triple-negative breast carcinoma(TNBC)characterized by lack estrogen receptor(ER), progesterone receptor(PR), and over-express human epidermal growth factor receptor 2(HER2), are mostly manifested as basal-like type, accounting for 7%-24% of all breast cancer. Compared with non-triple-negative breast, TNBC tends to behave more aggressively with, larger size, higher histologic grade, higher rate of metastasis and lower rate of disease-free survival. Owing to the lack of HER2 and hormonereceptor expression, TNBC does not respond to hormonal therapy or HER2-targeted agents. Fibroblast growth factor receptor1(FGFR1) is becoming a hotspot in TNBC research in recent years. FGFR1 over-expression is an important part contributing to apoptosis, proliferation, angiogenesis, distant metastasis and endocrine resistance. Neoangiogenesis is crucial to tumor progression of breast cancer invasion and metastasis, and is the result of several mechanistic processes including the vascular endothelial growth factor(VEGF) pathway. Compared with non-triple-negative cancers, TNBCs have significantly higher levels of VEGF. Studies about the expression and correlation of FGFR1 and VEGF in TNBC are not clear. The purposes of the study were to investigate the expression of FGFR1 and VEGF protein in TNBC, to analyze the correlation between FGFR1、VEGF with the clinical-pathological features and to analyze the association between them; and to identify the role of the clinical-pathological features in the prognosis of TNBC. Furthermore, to analyze the relationship of the expression of FGFR1 and VEGF in TNBC prognosis. Through these studies we hope to find some reliable molecular markers and therapeutic targets to promote the individualized treatment in TNBC patients.Methods: We adopted S-P immunohistochemical techniques to detect the positive expression of FGFR1、VEGF in 56 cases of TNBC. Pathological examinations were carried out by two pathologists at the Department of Pathology of Hebei General Hospital, which with complete clinical data from 2010-06-01 to 2011-12-30. Follow-up was performed by hospital visit, telephone or mail, and counted from the first day after surgery, and the patients’ death, the last follow-up time or lost as terminal point as the research time, which ended by 2014-12-30 or lost, the date of death. Finally, according to the follow-up data to analysiz the relationship of FGFR、VEGF in the prognosis in TNBC patients. SPSS13.0 statistical softw was adopted for statistical analysis. The clinical-pathological features data was determined by uesing χ2 test or Fisher’s Exact test. Spearman rank correlation was used to analysize the association between two variables. Kaplan-Meier method was performed to assess relapse-free survival(RFS), long-rank test and Cox proportional hazards were used to make monofactorial and multifactorial analysis. All statistical significance was set at the 0.05 level of significances.Results:1 In 56 TNBC cases tissue, the positive rates of expression of FGFR1 and VEGF was 19.64%(11/56) and 51.79%(29/56), respectively.2 In TNBC tissues, the expression of FGFR1 was not related with age, tumor size, lymph node metastasis, histological grade, clinical stage, vascular thrombosis, Basal-like stype and pathological type(P>0.05). The expression of VEGF was associated with lymph node metastasis(P<0.05). In comparision with Ⅰ~Ⅱstage, the expression of VEGF was a statistically higer in theⅢ stage,and the expression of VEGF in TNBC was associated with TNM stage(P<0.05).3 In 56 TNBC cases, the over-expression of FGFR1 and VEGF were 9 cases while the negative cases were 25 cases. The Spearman rank correlation revealed that the over-expression of FGFR1 was associated significantly with the positive expression of VEGF(r=0.297 P=0.026).4 Follow-up the 56 cases of TNBC patients, a total of 15 cases were recurrence, 12 cases in 3 years, accounting for 80.00%(12/15), the whole group of 3-year RFS was 78.57%. The main factors affecting the RFS for patients is lymph node metastasis, clinical stage, vascular invasion, the expression of FGFR1, VEGF(P<0.05). Multivariate analysis showed that: FGFR1 and clinical stage was significant independent risk factors for recurrence of TNBC patients(P<0.05).Conclusions:1 The expression of FGFR1 was foud no correlation with age, tumor size, lymph node metastasis, histological grade, clinical stage, vascular thrombosis, Basal-like stype and pathological type. The expression of VEGF was significant difference in lymph node metastasis, histological grade and TNM stage. On the contraty, there is no prominent relationship between VEGF protein expression with patients age, tumor size, vascular thrombosis, Basal-like stype and pathological type.2 The data analysis revealed that there was positive correlation between the expression of FGFR1 and VEGF, which determined that both proteins may be closely related with the malignant behavior of TNBC.3 Follow-up the 56 cases of TNBC patients, analysis the relationship of the clinical-pathological features in the prognosis of TNBC. Furthermore, to analyze the correlation of the expression of FGFR1 and VEGF in TNBC prognosis. And no significance difference was found between age, tumor size, histological grade, Basal-like stype and pathological type. Lymph node metastasis, clinical stage, vascular thrombosis and the positive expression of FGFR1,VEGF had significance with the prognosis of TNBC patients. Forward method for multivariate analysis showed that the clinical stage and FGFR1 protein associated significantly with RFS, they are independent prognostic factors in TNBC patients’ prognosis.