Department of Basic Pathology, National Defense Medical College, Tokorozawa 359-8513, Saitama, Japan.
Department of Pathology and Laboratory Medicine, National Defense Medical College, Tokorozawa, Japan.
BMC Cancer. 2022 Apr 2;22(1):361. doi: 10.1186/s12885-022-09363-0.
Tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) may be useful prognostic indicators in endometrial cancer. However, standardized assessment methods and the prognostic roles of these cells in different stage groups are unclear.
Formalin-fixed paraffin-embedded tissue samples of 107 endometrioid-type endometrial carcinomas (EECs) comprising 60 stage IB and 47 stage IIIC or IVB cases were evaluated. CD3 TILs, CD8 TILs, CD68 TAMs, and CD163 TAMs were detected by immunohistochemistry, and their densities were evaluated by semiquantitative and quantitative methods. TILs within tumor epithelial cell nests (E-TILs) and those within the stroma at the invasive front (S-TILs) were evaluated separately for CD3 and CD8 cells. The "TIL score" was defined as the sum of semiquantitative scores of CD3 E-TILs, CD3 S-TILs, CD8 E-TILs, and CD8 S-TILs. For TAMs, the area of CD68 and CD163 cells in the invasive margin were semiquantitatively and quantitatively evaluated. Clinicopathological and prognostic implications of TILs and TAMs in stage IB and IIIC/IVB EECs were examined by Cox univariate and multivariate analyses.
By Cox univariate analyses, semiquantitatively low CD3 E-TILs, low CD8 E-TILs, and low "TIL score" were significantly correlated with worse prognosis in stage IB patients (P = 0.011, 0.040, and 0.039, respectively). Likewise, low CD3 E-TILs and low CD8 E-TILs, by both semiquantitative (P = 0.011 and 0.0051) and quantitative evaluations (P < 0.0001, and P = 0.0015) and low "TIL score" (P = 0.020) were significantly correlated with worse prognosis in stage IIIC/IVB patients. By Cox multivariate analyses, semiquantitatively low CD3 E-TILs and low CD8 E-TILs, low "TIL score", and quantitatively low CD3 E-TILs and low CD8 E-TILs were independent worse prognostic factors in stage IIIC/IVB (P = 0.0011, 0.0053, 0.012, < 0.0001, and < 0.0001, respectively). CD68 or CD163 TAMs were not correlated with prognosis in any patients.
Both semiquantitatively and quantitatively low E-TILs, are correlated with worse prognosis in both early and advanced stage patients with EECs. In particular, CD3 E-TILs and CD8 E-TILs are potentially useful prognostic markers in patients with EEC regardless of the stage.
肿瘤浸润淋巴细胞（TILs）和肿瘤相关巨噬细胞（TAMs）可能是子宫内膜癌的有用预后指标。然而，标准化评估方法以及这些细胞在不同分期组中的预后作用尚不清楚。
评估了 107 例子宫内膜样型子宫内膜癌（EEC）的福尔马林固定石蜡包埋组织样本，包括 60 例 IB 期和 47 例 IIIC 或 IVB 期病例。通过免疫组织化学检测 CD3 TILs、CD8 TILs、CD68 TAMs 和 CD163 TAMs，并通过半定量和定量方法评估其密度。分别评估肿瘤上皮细胞巢内的 TILs（E-TILs）和侵袭前缘基质内的 TILs（S-TILs）中的 CD3 和 CD8 细胞。“TIL 评分”定义为 CD3 E-TILs、CD3 S-TILs、CD8 E-TILs 和 CD8 S-TILs 的半定量评分之和。对于 TAMs，通过半定量和定量方法评估 CD68 和 CD163 细胞在侵袭边缘的面积。通过 Cox 单因素和多因素分析，检查 TILs 和 TAMs 在 IB 期和 IIIC/IVB 期 EEC 中的临床病理和预后意义。
通过 Cox 单因素分析，半定量低 CD3 E-TILs、低 CD8 E-TILs 和低“TIL 评分”与 IB 期患者的预后不良显著相关（P=0.011、0.040 和 0.039）。同样，半定量（P=0.011 和 0.0051）和定量评估（P<0.0001 和 P=0.0015）低 CD3 E-TILs 和低 CD8 E-TILs，以及低“TIL 评分”（P=0.020）与 IIIC/IVB 期患者的预后不良显著相关。通过 Cox 多因素分析，半定量低 CD3 E-TILs 和低 CD8 E-TILs、低“TIL 评分”以及定量低 CD3 E-TILs 和低 CD8 E-TILs 是 IIIC/IVB 期的独立预后不良因素（P=0.0011、0.0053、0.012、<0.0001 和<0.0001）。CD68 或 CD163 TAMs 与任何患者的预后均无相关性。
E-TILs 的半定量和定量降低均与 EEC 早期和晚期患者的预后不良相关。特别是，CD3 E-TILs 和 CD8 E-TILs 是 EEC 患者潜在的有用预后标志物，与分期无关。
