PTEN、Twist1与肿瘤浸润淋巴细胞PD1的表达在三阴型乳腺癌中的临床病理意义

Clinicopathological significance of PTEN,Twist1 and PD1+tumor infiltration lymphocytes in triple negative breast cancer

目的:探讨PTEN、Twist1、PD1受体阳性肿瘤浸润淋巴细胞(PD1+ tumor infiltration lymphocytes,TILPD1)的表达与三阴型乳腺癌(triple negative breast cancer,TNBC)患者临床病理特征之间的关系。方法:收集20132018年蚌埠医学院第一附属医院诊断为TNBC标本76例,其他类型乳腺癌(NTNBC)标本47例,采用免疫组织化学方法检测、比较TNBC和NTNBC标本中PTEN、Twist1、TILPD1蛋白表达的差异,探讨其与患者临床病理特征及预后的关系。结果:TNBC样本肿瘤浸润淋巴细胞(tumor infiltrating lymphocytes,TIL)浸润程度更高(P<0.01)。TNBC中PTEN与Twist1及TILPD1的表达呈负相关(r=-0.314,P=0.012;r=-0.271,P=0.031),Twist1与TILPD1的表达呈正相关(r=0.281,P=0.019),TILPD1的表达与TIL浸润程度呈正相关(r=0.261,P=0.035)。PTEN与肿瘤的临床分期呈负相关(r=-0.380,P=0.002),与TIL浸润程度、肿瘤转移率、组织学分级也有一定的关联性。单因素及多因素生存分析显示TNM分期较小、无淋巴结及远处转移的患者预后更好;PTEN缺失表达与TILPD1高表达的患者预后不佳,是影响TNBC患者生存预后的独立危险因素。结论:PTEN与TILPD1的蛋白表达可能成为预测TNBC患者预后及疗效较为可靠的生物学标志。

Objective:To determine the expressions of PTEN,Twist1 and PD1+ tumor infiltration lymphocytes(TILPD1)and their clinicopathological significance in triple negative breast cancer(TNBC). Methods:Specimens of 76 TNBC patients and 46 other types of breast cancer patients(NTNBC)were collected from the First Affiliated Hospital of Bengbu Medical College. Expression levels of PTEN,Twist1 and TILPD1 proteins in the specimens were evaluated immunohistochemically and compared between the TNBC and NTNBC samples. Results:Higher degree of tumor infiltrating lymphocytes and higher level of Twist1 expression were found in the TNBC samples. In TNBC,expression PTEN was negatively correlated with those of Twist1 and TILPD1(r=-0.314,P=0.012;r=-0.271,P=0.031);expression level of Twist1 was positively correlated with that of TILPD1(r=0.281,P=0.019),and TILPD1 expression level was positively correlated with the degree of TIL infiltration(r=0.261,P=0.035). PTEN was negatively correlated with the clinical stage of the tumor(r=-0.380,P=0.002),and was also correlated with TIL infiltration degree,tumor metastasis rate and histological grade. Univariate and multivariate survival analyses showed that patients with lower TNM grade,without lymph node or distant metastasis had better clinical prognosis,while PTEN deficiency and high expression level of TILPD1 were independent risk factors for poor prognosis of TNBC.Conclusion:Expression levels of PTEN and TILPD1 proteins may be considered as biomarkers in predicting the prognostic of TNBC patients.