Prognostic significance of the programmed death ligand 1 expression in clear cell renal cell carcinoma and correlation with the tumor microenvironment and hypoxia-inducible factor expression
| العنوان: | Prognostic significance of the programmed death ligand 1 expression in clear cell renal cell carcinoma and correlation with the tumor microenvironment and hypoxia-inducible factor expression |
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| المؤلفون: | Hayriye Tatlı Doğan, Aydan Kilicarslan, Burak Bilgin, A. Ardicoglu, Ali Fuat Atmaca, Berrak Gumuskaya, Bulent Yalcin, Mehmet Ali Nahit Sendur, Merve Meryem Kiran |
| المساهمون: | Uşak Üniversitesi |
| المصدر: | Diagnostic Pathology, Vol 13, Iss 1, Pp 1-9 (2018) Diagnostic Pathology |
| بيانات النشر: | BMC, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Pathology, Lymphocyte, Nephrectomy, B7-H1 Antigen, 0302 clinical medicine, Renal cell carcinoma, PD-1, Basic Helix-Loop-Helix Transcription Factors, Tumor Microenvironment, Aged, 80 and over, Tissue microarray, biology, General Medicine, Middle Aged, Immunohistochemistry, Kidney Neoplasms, medicine.anatomical_structure, Hypoxia-inducible factors, 030220 oncology & carcinogenesis, Female, lcsh:RB1-214, Adult, PD-L1, medicine.medical_specialty, Histology, Pathology and Forensic Medicine, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, Biomarkers, Tumor, medicine, lcsh:Pathology, Humans, HIF, Carcinoma, Renal Cell, Aged, Retrospective Studies, Tumor microenvironment, business.industry, Research, Hypoxia-Inducible Factor 1, alpha Subunit, medicine.disease, Clear cell renal cell carcinoma, 030104 developmental biology, Tissue Array Analysis, biology.protein, Neoplasm Grading, business |
| الوصف: | PubMed ID: 30144808 Background: Clear cell renal cell carcinoma (ccRCC) is the most common renal malignancy. Hypoxia-inducible factors, HIF-1? and HIF-2?, are expressed in the majority of ccRCC. Targeting immune checkpoints with the blockade of PD-1 and its ligand PD-L1 reorganizes T-cell activity in tumor microenvironment and provides important antitumor responses. PD-L1 upregulation has been found to be hypoxia-inducible factor (HIF) dependent. Our aim is to demonstrate the association between PD-L1 and HIF expression and to reveal the role of PD-L1 in prognosis and its association with tumor microenvironment. Methods: Surgical specimens from 145 patients diagnosed with ccRCC, who had undergone radical or partial nephrectomy, were retrospectively analyzed. Immunohistochemistry on tissue microarrays (TMA) was performed to demonstrate expressions of PD-L1, HIF-1?, and HIF-2? in tumor cells and PD-1, CD4, and CD8 in lymphocytes to assess lymphocyte density in tumor microenvironment. Results: PD-L1 tumor cell expression was detected in 20/125 (13.8%) cases, which correlated with higher levels of PD-1, CD4, CD8 and HIF-2? expression. Low or high expression of HIF-1? was similar in PD-L1-positive cases. When PD-L1-positive cases were compared with negative ones, there was no significant difference in terms of prognostic factors. However, the number of WHO/ISUP grade 3-4 tumors was significantly higher in PD-L1-positive cases than in negative ones. Conclusion: PD-L1 tumor cell expression is strongly associated with increased HIF-2? expression and presence of dense lymphocytic infiltration in ccRCCs. Our findings confirm that PD-L1 positivity is associated with high ISUP nucleolar grade. The association between PD-L1, HIF, and lymphocyte density in tumor microenvironment must be clarified and especially taken into account in combination treatment. © 2018 The Author(s). |
| اللغة: | English |
| تدمد: | 1746-1596 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f3bf39665559c0c66b4f0d2eb79e14f8Test http://link.springer.com/article/10.1186/s13000-018-0742-8Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f3bf39665559c0c66b4f0d2eb79e14f8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17461596 |
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