Department of Pathology, Pusan National University Hospital, Biomedical Research Institution, Gudeok-ro, Seo-Gu, Busan, Republic of Korea.
Department of Pathology, Kosin University Gospel Hospital, Gamcheon-ro, Seo-gu, Busan, Republic of Korea.
PLoS One. 2019 Nov 19;14(11):e0224430. doi: 10.1371/journal.pone.0224430. eCollection 2019.
The prognostic significance of tumor-infiltrating lymphocytes has been determined in cancers of the lung, colon and breast, though there is no standardized method for using this prognostic indicator for lung cancer. We applied a modified version of the method proposed by the International Immuno-Oncology Biomarkers Working Group to primary lung adenocarcinoma, which uses histologic findings of hematoxylin and eosin sections. The study included a total cohort of 146 lung adenocarcinoma patients who underwent lobectomy with lymph node dissection at two hospitals between 2008 and 2012. The full-face sections of hematoxylin and eosin-stained slides were reviewed, and we evaluated the level of tumor-infiltrating lymphocytes as a percentage of the area occupied out of the total intra-tumoral stromal area. Histopathologic factors include histologic grade, necrosis, extracellular mucin, lymphovascular invasion, lymph node metastasis, level of tumor infiltrating lymphocytes, tertiary lymphoid structures around the tumor, and the presence of a germinal center in tertiary lymphoid structures. The high level of tumor-infiltrating lymphocytes was found to be significantly correlated with the histologic grade (p = 0.023), necrosis (p = 0.042), abundance of tertiary lymphoid structures(p<0.001) and presence of a germinal center in tertiary lymphoid structures (p = 0.004). A high level of tumor-infiltrating lymphocytes was associated with better progression-free survival (p = 0.011) as well as overall survival (p = 0.049). On multivariable analysis, high tumor-infiltrating lymphocyte levels were a good independent prognostic factor for progression-free survival (Hazard ratio: 0.389, 95% confidence interval: 0.161-0.941, p = 0.036). Histologic evaluation of tumor-infiltrating lymphocytes level in lung adenocarcinoma with H&E sections therefore has prognostic value in routine surgical pathology.
肿瘤浸润淋巴细胞的预后意义已在肺癌、结肠癌和乳腺癌中确定，但目前尚无标准化方法将这一预后指标用于肺癌。我们应用了国际免疫肿瘤生物标志物工作组提出的一种改良方法，该方法用于原发性肺腺癌，使用苏木精和伊红切片的组织学发现。该研究共纳入了 2008 年至 2012 年间在两家医院接受肺叶切除术和淋巴结清扫的 146 例肺腺癌患者。对苏木精和伊红染色切片的全切片进行了回顾，并评估了肿瘤浸润淋巴细胞在肿瘤内间质总面积中的百分比。组织病理学因素包括组织学分级、坏死、细胞外粘蛋白、血管淋巴管侵犯、淋巴结转移、肿瘤浸润淋巴细胞水平、肿瘤周围三级淋巴结构以及三级淋巴结构中是否存在生发中心。高肿瘤浸润淋巴细胞水平与组织学分级（p = 0.023）、坏死（p = 0.042）、三级淋巴结构丰富（p<0.001）和三级淋巴结构中存在生发中心（p = 0.004）显著相关。高肿瘤浸润淋巴细胞水平与无进展生存期（p = 0.011）和总生存期（p = 0.049）较好相关。多变量分析显示，高肿瘤浸润淋巴细胞水平是无进展生存期的良好独立预后因素（风险比：0.389，95%置信区间：0.161-0.941，p = 0.036）。因此，H&E 切片中肺腺癌肿瘤浸润淋巴细胞水平的组织学评估在常规外科病理学中具有预后价值。
