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Prognostic value of PD-1 and PD-L1 expression in patients with metastatic clear cell renal cell carcinoma.
Urol Oncol. 2018 11; 36(11):499.e9-499.e16.UO

Abstract

OBJECTIVE

In renal cell carcinoma (RCC), several prognostic biomarkers have been identified and are under investigation. Several reports have shown that the expression of programmed death 1 (PD-1) and its ligand PD-L1 is associated with poor outcome for patients with RCC. The present study is aimed at evaluating the expression of PD-1 and PD-L1 and to investigate their clinical and prognostic significance in patients with clear cell RCC (CCRCC) having received molecular targeted therapies. In addition, we also evaluated the relationship between the expression of PD-1 and PD-L1 and intratumoral tumor infiltrating lymphocytes (TILs).

METHODS

A total of 33 patients with metastatic CCRCC who underwent surgery and received molecular targeted therapies from March 2008 to April 2016 were retrospectively reviewed and analyzed. Tissue specimens from the patients were analyzed for PD-1 and PD-L1 expression by immunohistochemistry.

RESULTS

The median patient age was 64 years old (range=53-78). The majority of patients were male (81.8%). All Memorial Sloan Kettering Cancer Center risk groups were represented among the patients with 39.4% with favorable-, 51.5% with intermediate- and 9.1% with poor-risk. The expression of PD-1 and PD-L1 was observed in 16 (48.5%) and 9 (27.3%) patients, respectively. The expression of PD-1 and PD-L1 was associated with a larger primary renal tumor size, higher nuclear grade and sarcomatoid feature. Kaplan-Meier analysis revealed that no significant difference in progression free survival of first line molecular targeted therapy was found for PD-1 (P=0.2396) and PD-L1 (P=0.5919) expression. However, PD-1 expression has a significant worse impact on overall survival (OS) (P=0.0385), while for PD-L1 expression only a trend is seen for OS (P=0.1542). The patients with PD-1 and PD-L1 expression showed higher infiltration of CD4 (P<0.0001 and P<0.0001, respectively), CD8 (P=0.0328 and P=0.0044, respectively) and FOXP3 (P<0.0001 and P=0.0033, respectively) positive TILs.

CONCLUSION

PD-1 and PD-L1 expression is significantly associated with adverse clinicopathological features in CCRCC. Furthermore, PD-1 expression could be one of the biomarkers suggesting poor outcome in patients with metastatic CCRCC receiving molecular targeted therapies.

Authors+Show Affiliations

Department of Urology, Kurume University School of Medicine, Kurume, Japan. Electronic address: ueda_kousuke@med.kurume-u.ac.jp.Department of Urology, Kurume University School of Medicine, Kurume, Japan.Department of Urology, Kurume University School of Medicine, Kurume, Japan.Department of Urology, Kurume University School of Medicine, Kurume, Japan.Department of Urology, Kurume University School of Medicine, Kurume, Japan.Department of Urology, Kurume University School of Medicine, Kurume, Japan.Department of Urology, Kurume University School of Medicine, Kurume, Japan.Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan.Department of Pathology, Kurume University School of Medicine, Kurume, Japan.Department of Urology, Kurume University School of Medicine, Kurume, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30131293

Citation

Ueda, Kosuke, et al. "Prognostic Value of PD-1 and PD-L1 Expression in Patients With Metastatic Clear Cell Renal Cell Carcinoma." Urologic Oncology, vol. 36, no. 11, 2018, pp. 499.e9-499.e16.
Ueda K, Suekane S, Kurose H, et al. Prognostic value of PD-1 and PD-L1 expression in patients with metastatic clear cell renal cell carcinoma. Urol Oncol. 2018;36(11):499.e9-499.e16.
Ueda, K., Suekane, S., Kurose, H., Chikui, K., Nakiri, M., Nishihara, K., Matsuo, M., Kawahara, A., Yano, H., & Igawa, T. (2018). Prognostic value of PD-1 and PD-L1 expression in patients with metastatic clear cell renal cell carcinoma. Urologic Oncology, 36(11), e9-e16. https://doi.org/10.1016/j.urolonc.2018.07.003
Ueda K, et al. Prognostic Value of PD-1 and PD-L1 Expression in Patients With Metastatic Clear Cell Renal Cell Carcinoma. Urol Oncol. 2018;36(11):499.e9-499.e16. PubMed PMID: 30131293.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prognostic value of PD-1 and PD-L1 expression in patients with metastatic clear cell renal cell carcinoma. AU - Ueda,Kosuke, AU - Suekane,Shigetaka, AU - Kurose,Hirofumi, AU - Chikui,Katsuaki, AU - Nakiri,Makoto, AU - Nishihara,Kiyoaki, AU - Matsuo,Mitsunori, AU - Kawahara,Akihiko, AU - Yano,Hirohisa, AU - Igawa,Tsukasa, Y1 - 2018/08/18/ PY - 2017/12/20/received PY - 2018/05/14/revised PY - 2018/07/10/accepted PY - 2018/8/23/pubmed PY - 2019/1/19/medline PY - 2018/8/23/entrez KW - Molecular targeted therapy KW - PD-1, PD-L1 KW - Renal cell carcinoma KW - Tumor infiltrating lymphocytes SP - 499.e9 EP - 499.e16 JF - Urologic oncology JO - Urol Oncol VL - 36 IS - 11 N2 - OBJECTIVE: In renal cell carcinoma (RCC), several prognostic biomarkers have been identified and are under investigation. Several reports have shown that the expression of programmed death 1 (PD-1) and its ligand PD-L1 is associated with poor outcome for patients with RCC. The present study is aimed at evaluating the expression of PD-1 and PD-L1 and to investigate their clinical and prognostic significance in patients with clear cell RCC (CCRCC) having received molecular targeted therapies. In addition, we also evaluated the relationship between the expression of PD-1 and PD-L1 and intratumoral tumor infiltrating lymphocytes (TILs). METHODS: A total of 33 patients with metastatic CCRCC who underwent surgery and received molecular targeted therapies from March 2008 to April 2016 were retrospectively reviewed and analyzed. Tissue specimens from the patients were analyzed for PD-1 and PD-L1 expression by immunohistochemistry. RESULTS: The median patient age was 64 years old (range=53-78). The majority of patients were male (81.8%). All Memorial Sloan Kettering Cancer Center risk groups were represented among the patients with 39.4% with favorable-, 51.5% with intermediate- and 9.1% with poor-risk. The expression of PD-1 and PD-L1 was observed in 16 (48.5%) and 9 (27.3%) patients, respectively. The expression of PD-1 and PD-L1 was associated with a larger primary renal tumor size, higher nuclear grade and sarcomatoid feature. Kaplan-Meier analysis revealed that no significant difference in progression free survival of first line molecular targeted therapy was found for PD-1 (P=0.2396) and PD-L1 (P=0.5919) expression. However, PD-1 expression has a significant worse impact on overall survival (OS) (P=0.0385), while for PD-L1 expression only a trend is seen for OS (P=0.1542). The patients with PD-1 and PD-L1 expression showed higher infiltration of CD4 (P<0.0001 and P<0.0001, respectively), CD8 (P=0.0328 and P=0.0044, respectively) and FOXP3 (P<0.0001 and P=0.0033, respectively) positive TILs. CONCLUSION: PD-1 and PD-L1 expression is significantly associated with adverse clinicopathological features in CCRCC. Furthermore, PD-1 expression could be one of the biomarkers suggesting poor outcome in patients with metastatic CCRCC receiving molecular targeted therapies. SN - 1873-2496 UR - https://www.unboundmedicine.com/medline/citation/30131293/Prognostic_value_of_PD_1_and_PD_L1_expression_in_patients_with_metastatic_clear_cell_renal_cell_carcinoma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1078-1439(18)30251-5 DB - PRIME DP - Unbound Medicine ER -