肿瘤浸润淋巴细胞及肿瘤细胞EGFR蛋白表达在三阴性乳腺癌患者中的预后价值

Prognostic Value of Tumor Infiltrating-Lymphocytes and EGFR Protein Expression of Tumor Cell in Patients with Triple-Negative Breast Cancer

摘要: 与Luminal型乳腺癌、人类表皮生长因子受体2 (HER2) (+)乳腺癌相比，三阴性乳腺癌(Triple-Negative Breast Cancer, TNBC)缺乏靶向治疗的特异性靶点，具有生物学侵袭性、复发转移风险高、生存期较短等特点。目的：评估肿瘤浸润淋巴细胞(Tumor Infiltrating-Lymphocytes, TILs)与表皮生长因子受体(EGFR)表达的预后价值，并确定它们与TNBC的临床病理参数之间的关系。材料与方法：收集2010年1月至2015年12月共计70例于青岛大学附属医院接受手术治疗的、有病理报告和临床资料完整的TNBC患者。评估手术标本中TILs比例，并分为高比例(TILs ≥ 40%，n = 28)和低比例(TILs < 40%，n = 42) 2组。免疫组化检测ER、PR、HER2和EGFR的表达，评估EGFR表达情况，并将其分为强阳性组(EGFR ≥ 50%，n = 10)和非强阳性组(EGFR < 50%，n = 60)。评估TILs比例和EGFR表达对预后的影响。结果：TILs低比例组中位无病生存期(DFS) 55.5个月，TILs高比例组97个月，两组比较p = 0.059；TILs低比例组中位总生存期(OS) 69.5个月，高比例组97个月，p = 0.084。EGFR非强阳性组，低比例TILs (TILs < 40%, n = 25)中位DFS和OS分别为24个月和36个月，高比例TILs (TILs ≥ 40%, n = 35)中位DFS和OS均为96个月，不同TILs比例组之间DFS (p = 0.035)和OS (p = 0.048)具有统计学显著性差异；EGFR强阳性组，低比例TILs (TILs < 40%, n = 7)中位DFS和OS均为98个月，高比例TILs (TILs ≥ 40%, n = 3)中位DFS和OS均为94个月(p = 0.513和p = 0.882)。结论：不同TILs比例三阴性乳腺癌患者治疗后DFS和OS差别无统计学显著性。EGFR非强阳性的TNBC患者，TILs比例越高、术后DFS和OS均越长。

Abstract: Compared with Luminal breast cancer and HER2 (+) breast cancer, triple-negative breast cancer (TNBC) lacks specific targets for targeted therapy, and is characterized by biological invasions, high risk of recurrence and metastasis, and short survival. Objective: To evaluate the prognostic value of tumor infiltrating-lymphocytes (TILs) and epidermal growth factor receptor (EGFR) expression, and to determine their relationship with clinicopathological parameters of TNBC. Materials and Methods: 70 TNBC patients with complete pathological reports and clinical data between January 2010 to December 2015 in Affiliated Hospital of Qingdao University were selected. TILs proportions in sur-gical specimens were assessed and divided into high (TILs ≥ 40%, n = 28) and low groups (TILs < 40%, n = 42). The expression of ER, PR, HER2 and EGFR were detected by immunohistochemistry. EGFR expression was evaluated and divided into strongly positive group (EGFR ≥ 50%, n = 10) and non-strongly positive group (EGFR < 50%, n = 60). The effect of TILs ratio and EGFR expression on prognosis was evaluated. Results: Median disease-free survival (DFS) and total survival (OS) were 55.5 and 69.5 months, respectively, in the low-proportion TILs group, and both of them were 97 months in the high-proportion TILs group. There were no statistically significant differences in DFS (p = 0.059) and OS (p = 0.084) in different TILs proportion groups. In EGFR non-strongly positive group, median DFS and OS were 24 and 36 months, respectively, in the low-proportion TILs group (TILs < 40%, n = 25). Median DFS and OS were 96 months in the high-proportion TILs group (TILs ≥ 40%, n = 35). There were statistically significant differences in DFS (p = 0.035) and OS (p = 0.048) in different TILs proportion groups. In EGFR positive group, median DFS and OS were 98 months in the low-proportion TILs group (TILs < 40%, n = 7), and median DFS and OS were 94 months in the high-proportion TILs (TILs ≥ 40%, n = 3) (p = 0.513 and p = 0.882). Conclusion: TILs ratio and EGFR expression had no significant effect on post operative DFS and OS in patients with triple negative breast cancer. In TNBC patients without strong EGFR, the higher the proportion of TILs, the longer the postoperative DFS and OS.