Lancashire Teaching Hospitals Foundation NHS Trust, Lancashire, UK.
Department of Oncology, University of Cambridge, Cambridge, UK.
BMC Cancer. 2017 Sep 20;17(1):657. doi: 10.1186/s12885-017-3585-x.
There is evidence that some ovarian tumours evoke an immune response, which can be assessed by tumour infiltrating lymphocytes (TILs). To facilitate adoption of TILs as a clinical biomarker, a standardised method for their H&E visual evaluation has been validated in breast cancer.
We sought to investigate the prognostic significance of TILs in a study of 953 invasive epithelial ovarian cancer tumour samples, both primary and metastatic, from 707 patients from the prospective population-based SEARCH study. TILs were analysed using a standardised method based on H&E staining producing a percentage score for stromal and intratumoral compartments. We used Cox regression to estimate hazard ratios of the association between TILs and survival.
The extent of stromal and intra-tumoral TILs were correlated in the primary tumours (n = 679, Spearman's rank correlation = 0.60, P < 0.001) with a similar correlation in secondary tumours (n = 224, Spearman's rank correlation = 0.62, P < 0.001). There was a weak correlation between stromal TIL levels in primary and secondary tumour samples (Spearman's rank correlation = 0.29, P < 0.001) and intra-tumoral TIL levels in primary and secondary tumour samples (Spearman's rank correlation = 0.19, P = 0.0094). The extent of stromal TILs differed between histotypes (Pearson chi2 (12d.f.) 54.1, P < 0.0001) with higher levels of stromal infiltration in the high-grade serous and endometriod cases. A significant association was observed for higher intratumoral TIL levels and a favourable prognosis (HR 0.74 95% CI 0.55-1.00 p = 0.047).
This study is the largest collection of epithelial ovarian tumour samples evaluated for TILs. We have shown that stromal and intratumoral TIL levels are correlated and that their levels correlate with clinical variables such as tumour histological subtype. We have also shown that increased levels of both intratumoral and stromal TILs are associated with a better prognosis; however, this is only statistically significant for intratumoral TILs. This study suggests that a clinically useful immune prognostic indicator in epithelial ovarian cancer could be developed using this technique.
有证据表明，一些卵巢肿瘤会引发免疫反应，这可以通过肿瘤浸润淋巴细胞（TILs）来评估。为了促进 TILs 作为临床生物标志物的应用，已经在乳腺癌中验证了一种用于其 H&E 视觉评估的标准化方法。
我们旨在通过对来自前瞻性基于人群的 SEARCH 研究的 707 名患者的 953 例原发性和转移性侵袭性上皮性卵巢癌肿瘤样本进行研究，来探讨 TILs 的预后意义。使用基于 H&E 染色的标准化方法分析 TILs，产生间质和肿瘤内部分的百分比评分。我们使用 Cox 回归估计 TILs 与生存之间的关联的风险比。
在原发性肿瘤（n=679）中，间质和肿瘤内 TILs 的程度呈正相关（Spearman 秩相关=0.60，P<0.001），继发性肿瘤（n=224）也存在类似的相关性（Spearman 秩相关=0.62，P<0.001）。原发性和继发性肿瘤样本的间质 TIL 水平之间存在弱相关性（Spearman 秩相关=0.29，P<0.001），原发性和继发性肿瘤样本的肿瘤内 TIL 水平之间也存在弱相关性（Spearman 秩相关=0.19，P=0.0094）。组织类型之间间质 TILs 的程度存在差异（Pearson chi2（12d.f.）54.1，P<0.0001），高级别浆液性和子宫内膜样病例的间质浸润水平更高。较高的肿瘤内 TIL 水平与较好的预后呈显著相关（HR 0.74 95%CI 0.55-1.00 p=0.047）。
本研究是评估 TILs 的最大上皮性卵巢肿瘤样本集。我们已经表明，间质和肿瘤内 TIL 水平呈正相关，并且它们的水平与肿瘤组织学亚型等临床变量相关。我们还表明，肿瘤内和间质 TIL 水平的升高与更好的预后相关；然而，这仅在肿瘤内 TIL 方面具有统计学意义。这项研究表明，使用这种技术可以开发出一种在卵巢上皮性癌中具有临床应用价值的免疫预后指标。
