Adelaide Pladys

Independent association of PD-L1 expression with noninactivated VHL clear cell renal cell carcinoma-A finding with therapeutic potential.

Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor that is characterized in most cases by inactivation of the tumor suppressor gene VHL. The VHL/HIF/VEGF pathway thus plays a major role in angiogenesis and is currently targeted by anti‐angiogenic therapy. The emergence of resistance is leading to the use of targeted immunotherapy against immune checkpoint PD1/PDL1 that restores antitumor immune response. The correlation between VHL status and PD‐L1 expression has been little investigated. In this study, we retrospectively reviewed 98 consecutive cases of ccRCC and correlated PD‐L1 expression by immunohistochemistry (IHC) with clinical data (up to 10‐year follow‐up), pathological criteria, VEGF, PAR‐3, CAIX and PD‐1 expressions by IHC and complete VHL status (deletion, mutation and promoter hypermethylation). PD‐L1 expression was observed in 69 ccRCC (70.4%) and the corresponding patients had a worse prognosis, with a median specific survival of 52 months (p = 0.03). PD‐L1 expression was significantly associated with poor prognostic factors such as a higher ISUP nucleolar grade (p = 0.01), metastases at diagnosis (p = 0.01), a sarcomatoid component (p = 0.04), overexpression of VEGF (p = 0.006), and cytoplasmic PAR‐3 expression (p = 0.01). PD‐L1 expression was also associated with dense PD‐1 expression (p = 0.007) and with ccRCC with 0 or 1 alteration(s) (non‐inactivated VHL tumors; p = 0.007) that remained significant after multivariate analysis (p = 0.004 and p = 0.024, respectively). Interestingly, all wild‐type VHL tumors (no VHL gene alteration, 11.2%) expressed PD‐L1. In this study, we found PD‐L1 expression to be associated with noninactivated VHL tumors and in particular wild‐type VHL ccRCC, which may benefit from therapies inhibiting PD‐L1/PD‐1.

Correction to: Deleterious effects of dialysis emergency start, insights from the French REIN registry

Following publication of the original article [1], the authors reported that all of the authors’ names were processed incorrectly so that their given and family names were interchanged.

Synchronous Metastatic Clear-Cell Renal Cell Carcinoma: A Distinct Morphologic, Immunohistochemical, and Molecular Phenotype

&NA; In order to compare synchronous and metachronous metastatic clear cell renal cell carcinoma, we performed a pathologic, immunohistochemical, and molecular study on primary tumors in a retrospective series of 48 consecutive patients with up to 10 years of follow‐up. Synchronous metastatic clear cell renal cell carcinoma had a distinct phenotype that may explain their worse prognosis. Introduction: Clear cell renal cell carcinomas (ccRCCs) are highly metastatic tumors with metastases detected at diagnosis (synchronous) or during follow‐up (metachronous). To date, there have been no reports comparing primary ccRCC of patients with synchronous and metachronous metastases, who are different in terms of prognosis. Determining whether there is a phenotypic difference between these 2 groups could have important clinical implications. Patients and Methods: In a retrospective consecutive cohort of 98 patients with ccRCC, 48 patients had metastases, including 28 synchronous and 20 metachronous presentations, with a follow‐up of 10 years. For each primary tumor in these metastatic patients, pathologic criteria, expression of vascular endothelial growth factor, partitioning‐defective 3, CAIX, and programmed death ligand 1 as detected by immunohistochemistry, and complete VHL status were analyzed. Univariate analysis was performed, and survival was assessed using Kaplan‐Meier curves compared by log‐rank test. Results: Compared with primary ccRCC in patients with metachronous metastases, primary ccRCC in patients with synchronous metastases were significantly associated with a poorer Eastern Cooperative Oncology Group performance (P = .045), higher pT status (P = .038), non‐inactivated VHL gene (P = .01), sarcomatoid component (P = .007), expression of partitioning‐defective 3 (P = .007), and overexpressions of vascular endothelial growth factor (> 50%) (P = .017) and programmed death ligand 1 (P = .019). Patients with synchronous metastases had a worse cancer‐specific survival than patients with metachronous metastases even from metastatic diagnosis (median survival, 16 months vs. 46 months, respectively; P = .01). Conclusion: This long‐term study is the first to support the notion that synchronous m‐ccRCC has a distinct phenotype. This is probably linked to the occurrence of oncogenic events that could explain the worse prognosis. These particular patients with metastases could benefit from specific therapy.