The prognostic significance of tumor-infiltrating lymphocytes assessment with hematoxylin and eosin sections in resected primary lung adenocarcinoma

Autoři: Ahrong Kim aff001;  So Jeong Lee aff001;  Jihyun Ahn aff002;  Won Young Park aff001;  Dong Hoon Shin aff003;  Chang Hun Lee aff001;  Hoon Kwon aff004;  Yeon Joo Jeong aff004;  Hyo Yeong Ahn aff005;  Hoseok I aff005;  Yeong Dae Kim aff005;  Jeong Su Cho aff005
Působiště autorů: Department of Pathology, Pusan National University Hospital, Biomedical Research Institution, Gudeok-ro, Seo-Gu, Busan, Republic of Korea aff001;  Department of Pathology, Kosin University Gospel Hospital, Gamcheon-ro, Seo-gu, Busan, Republic of Korea aff002;  Department of Pathology, Yangsan Pusan National University Hospital, Beomeori, Mulgeum-eop, Kyeong-Nam, Republic of Korea aff003;  Department of Radiology, Pusan National University Hospital, Biomedical Research Institution, Gudeok-ro, Seo-Gu, Busan, Republic of Korea aff004;  Department of Thoracic and Cardiovascular Surgery, Pusan National University Hospital, Biomedical Research Institution, Gudeok-ro, Seo-Gu, Busan, Republic of Korea aff005
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224430


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.

Klíčová slova:

Adenocarcinoma of the lung – Adenocarcinomas – Histology – Invasive tumors – Lung and intrathoracic tumors – Non-small cell lung cancer – Secondary lung tumors – Tumor-infiltrating lymphocytes


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