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

Autor: Hayriye Tatlı Doğan, Aydan Kilicarslan, Burak Bilgin, A. Ardicoglu, Ali Fuat Atmaca, Berrak Gumuskaya, Bulent Yalcin, Mehmet Ali Nahit Sendur, Merve Meryem Kiran
Přispěvatelé: Uşak Üniversitesi
Jazyk: angličtina
Rok vydání: 2018
Předmět:
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
Zdroj: Diagnostic Pathology, Vol 13, Iss 1, Pp 1-9 (2018)
Diagnostic Pathology
ISSN: 1746-1596
DOI: 10.1186/s13000-018-0742-8
Popis: 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).
Databáze: OpenAIRE
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