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目的叉头框转录因子P3(forkhead box P3,FOXP3)属于叉头框/翼状螺旋转录因子(forkhead box,FOX)家族成员,早期被认为特异性表达于免疫抑制性CD4+CD25+调节性T细胞(CD4+CD25+regulatory T cell,Treg)。而近些年来研究发现,FOXP3在多种肿瘤细胞中均有表达。本研究旨在探讨FOXP3在乳腺浸润性导管癌组织中的表达与临床病理学特征的关系及其预后意义。方法收集2009-01-01-2012-04-30河北医科大学第四医院乳腺中心收治的123例乳腺浸润性导管癌标本,采用免疫组织化学法检测FOXP3蛋白的表达,分析FOXP3与肿瘤临床病理学特征间的关系,并采用Kaplan-Meier法及Cox比例回归风险模型进行生存分析。结果 FOXP3蛋白在乳腺浸润性导管癌实质细胞质和细胞核中均有表达,FOXP3总表达率为68.29%(84/123)。生存分析结果显示,FOXP3表达阳性组的无病生存率(disease free survival,DFS)为89.29%,高于阴性组的71.79%,差异有统计学意义,χ~2=6.119,P=0.013;但2组的总生存率(overall survival,OS)差异无统计学意义,χ~2=1.911,P=0.167。进一步分析FOXP3在乳腺癌细胞中的表达部位发现,FOXP3在细胞核中表达率为47.97%(59/123),细胞质中为63.41%(78/123)。生存分析结果显示,FOXP3细胞核表达阳性组的OS和DFS分别为94.92%和91.53%,均高于细胞核阴性组的82.81%和76.56%,差异均有统计学意义,χ~2值分别为5.265和4.974,P值分别为0.022和0.026;且Cox多因素分析结果显示,细胞核FOXP3是改善OS的独立预后因素,HR=0.245,P=0.033;但细胞质FOXP3与预后无明显相关性。在FOXP3细胞核表达阳性患者中,无脉管瘤栓组(χ~2=5.117,P=0.024)及Ki-67低表达组(χ~2=4.214,P=0.041)的表达率更高;且各分子分型间表达率差异有统计学意义,χ~2=12.983,P=0.002;在Luminal A型乳腺癌中FOXP3细胞核表达率最高,为68.18%。结论FOXP3在乳腺浸润性导管癌中的预后意义与表达部位相关,细胞核FOXP3高表达是改善乳腺癌OS的独立预后因素,而细胞质FOXP3的表达意义尚不明确。细胞核FOXP3可作为乳腺癌预后良好的预测指标。
Objective Forkhead box P3 (FOXP3) is a member of the forkhead box (FOX) family and was initially thought to be specifically expressed in immunosuppressive CD4 + CD25 + regulatory T cells ( CD4 + CD25 + regulatory T cell, Treg). In recent years, studies have found that FOXP3 are expressed in a variety of tumor cells. This study was designed to investigate the relationship between the expression of FOXP3 in breast invasive ductal carcinoma and clinicopathological features and its prognostic significance. Methods A total of 123 invasive ductal carcinomas of the breast were collected from the Breast Center of the Fourth Hospital of Hebei Medical University from January 2009 to January 01, 2009. The expression of FOXP3 protein was detected by immunohistochemistry. The correlation between FOXP3 and clinicopathology The relationship between the characteristics and Kaplan-Meier method and Cox proportional hazards regression model for survival analysis. Results FOXP3 protein was expressed in the cytoplasm and nucleus of breast invasive ductal carcinoma. The total FOXP3 expression rate was 68.29% (84/123). Survival analysis showed that the disease free survival (DFS) of FOXP3 positive group was 89.29%, which was higher than that of negative group (71.79%), the difference was statistically significant (χ ~ 2 = 6.119, P = 0.013) There was no significant difference in overall survival (OS) between the two groups (χ ~ 2 = 1.911, P = 0.167). Further analysis of FOXP3 expression in breast cancer cells showed that FOXP3 expression in the nucleus was 47.97% (59/123), cytoplasm was 63.41% (78/123). Survival analysis showed that the OS and DFS of FOXP3 positive cells were 94.92% and 91.53%, respectively, which were higher than those of the negative cells (82.81% and 76.56%), the differences were statistically significant (χ ~ 2 = 5.265 and 4.974, P values were 0.022 and 0.026 respectively. Cox multivariate analysis showed that nuclear FOXP3 was an independent prognostic factor for improving OS, HR = 0.245, P = 0.033; however, there was no significant correlation between FOXP3 and prognosis. In the patients with positive FOXP3 nucleus expression, the expression rate was higher in the non-vascular suppository group (χ ~ 2 = 5.117, P = 0.024) and Ki-67 low expression group (χ ~ 2 = 4.214, P = 0.041) There was significant difference in the expression rates of various molecular types (χ ~ 2 = 12.983, P = 0.002). The highest nuclear expression rate of FOXP3 in Luminal A breast cancer was 68.18%. Conclusions The prognostic significance of FOXP3 in breast invasive ductal carcinoma is related to the expression of FOXP3. The high expression of FOXP3 in nucleus is an independent prognostic factor for OS in breast cancer. The significance of FOXP3 expression in the cytoplasm is unclear. Nuclear FOXP3 can be used as a good predictor of breast cancer prognosis.