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Reliability of a single-region sample to evaluate tumor immune microenvironment in hepatocellular carcinoma.
Shen, Ying-Chun; Hsu, Chia-Lang; Jeng, Yung-Ming; Ho, Ming-Chih; Ho, Cheng-Maw; Yeh, Ching-Ping; Yeh, Chia-Yu; Hsu, Meng-Chi; Hu, Ray-Heng; Cheng, Ann-Lii.
Afiliação
  • Shen YC; Department of Medical Oncology, National Taiwan University Cancer Center, Taiwan; Department of Oncology, National Taiwan University Hospital, Taiwan; Graduate Institute of Oncology, School of Medicine, National Taiwan University, Taiwan.
  • Hsu CL; Graduate Institute of Oncology, School of Medicine, National Taiwan University, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taiwan.
  • Jeng YM; Department of Pathology, National Taiwan University Hospital, Taiwan.
  • Ho MC; Department of Surgery, National Taiwan University Hospital, Taiwan.
  • Ho CM; Department of Surgery, National Taiwan University Hospital, Taiwan.
  • Yeh CP; Department of Oncology, National Taiwan University Hospital, Taiwan.
  • Yeh CY; Department of Oncology, National Taiwan University Hospital, Taiwan.
  • Hsu MC; Department of Oncology, National Taiwan University Hospital, Taiwan.
  • Hu RH; Department of Surgery, National Taiwan University Hospital, Taiwan.
  • Cheng AL; Department of Medical Oncology, National Taiwan University Cancer Center, Taiwan; Department of Oncology, National Taiwan University Hospital, Taiwan; Graduate Institute of Oncology, School of Medicine, National Taiwan University, Taiwan. Electronic address: alcheng@ntu.edu.tw.
J Hepatol ; 72(3): 489-497, 2020 03.
Article em En | MEDLINE | ID: mdl-31634533
BACKGROUND & AIMS: Intratumor heterogeneity has frequently been reported in patients with hepatocellular carcinoma (HCC). Thus, the reliability of single-region tumor samples for evaluation of the tumor immune microenvironment is also debatable. We conducted a prospective study to analyze the similarity in tumor immune microenvironments among different regions of a single tumor. METHODS: Multi-region sampling was performed on newly resected tumors. The tumor immune microenvironment was evaluated by immunohistochemical staining of PD-L1, CD4, CD8, CD20, FoxP3, DC-LAMP (or LAMP3), CD68, MPO, and tertiary lymphoid structures (TLSs). PD-L1 expression was manually quantified according to the percentage of PD-L1-stained tumor or stromal cells. The densities (number/mm2) of immune cells and the number of TLSs per sample were determined by whole-section counting. RNA-sequencing was applied in selected samples. Similarities in tumor immune microenvironments within each tumor were evaluated by multivariate Mahalanobis distance analyses. RESULTS: Thirteen tumors were collected from 12 patients. The median diameter of tumors was 9 cm (range 3-16 cm). A median of 6 samples (range 3-12) were obtained from each tumor. Nine (69.2%) tumors exhibited uniform expression of PD-L1 in all regions of the tumor. Out of 13 tumors analyzed by immunohistochemical staining, 8 (61.5%) tumors displayed a narrow Mahalanobis distance for all regions within the tumor; while 8 (66.7%) of the 12 tumors analyzed by RNA-sequencing displayed a narrow Mahalanobis distance. Immunohistochemistry and RNA-sequencing had a high concordance rate (83.3%; 10 of 12 tumors) for the evaluation of similarities between tumor immune microenvironments within a tumor. CONCLUSIONS: A single-region tumor sample might be reliable for the evaluation of tumor immune microenvironments in approximately 60-70% of patients with HCC. LAY SUMMARY: Heterogeneity in the regional immune microenvironments of tumors has been reported in patients with hepatocellular carcinoma. This heterogeneity could be an obstacle when trying to reliably evaluate the immune microenvironment of an entire tumor using only a single-region tumor sample, which may be the only option in patients with more advanced disease. Our study utilized both immunohistochemical and transcriptomic analyses to demonstrate that a single-region sample is reliable for evaluation of tumor immune microenvironments in 60-70% of patients with hepatocellular carcinoma.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Microambiente Tumoral / Antígeno B7-H1 / Estruturas Linfoides Terciárias / Neoplasias Hepáticas Tipo de estudo: Observational_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Hepatol Assunto da revista: GASTROENTEROLOGIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Taiwan

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Microambiente Tumoral / Antígeno B7-H1 / Estruturas Linfoides Terciárias / Neoplasias Hepáticas Tipo de estudo: Observational_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Hepatol Assunto da revista: GASTROENTEROLOGIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Taiwan