The Clinical and Molecular Features in the VHL Renal Cancers; Close or Distant Relatives with Sporadic Clear Cell Renal Cell Carcinoma?

Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited cancer syndrome caused by germline mutations in the VHL tumor suppressor gene, characterized by the susceptibility to a wide array of benign and malign neoplasms, including clear-cell renal cell carcinoma. Moreover, VHL somatic inactivation is a crucial molecular event also in sporadic ccRCCs tumorigenesis. While systemic biomarkers in the VHL syndrome do not currently play a role in clinical practice, a new promising class of predictive biomarkers, microRNAs, has been increasingly studied. Lots of pan-genomic studies have deeply investigated the possible biological role of microRNAs in the development and progression of sporadic ccRCC; however, few studies have investigated the miRNA profile in VHL patients. Our review summarize all the new insights related to clinical and molecular features in VHL renal cancers, with a particular focus on the overlap with sporadic ccRCC.

Renal Function Outcomes in Metastatic Non-Small-Cell Lung Carcinoma Patients Treated with Chemotherapy or Immune Checkpoint Inhibitors: An Unexpected Scenario.

Immune checkpoint inhibitors (ICIs) and platinum-based chemotherapy (CT) are effective therapeutic agents for the palliative treatment of metastatic non-small-cell lung cancer (NSCLC); the aim of our study was to investigate the acute and chronic renal toxicities in this setting. We collected data on 292 patients who received cisplatin (35%), carboplatin-based regimens (25%), or ICI monotherapy (40%). The primary and secondary outcomes were compared to the acute kidney injury (AKI) rate and the mean estimated GFR (eGFR) decay between groups, respectively, over a mean follow-up duration of 15 weeks. We observed 26 AKI events (8.9%), mostly stage I AKI (80.7%); 15% were stage II AKI, 3.8% were stage III, and none required renal replacement therapy or ICU admission. The AKI rates were 10.9%, 6.8%, and 8.9% for the cisplatin, carboplatin, and ICI groups, respectively, and no significant differences were observed between the groups (p = 0.3). A global mean eGFR decay of 2.2 mL/min was observed, while for the cisplatin, carboplatin, and ICI groups, the eGFR decay values were 2.3 mL/min, 1.1 mL/min, and 3.5 mL/min, respectively. No significant differences were observed between the groups. Cisplatin/carboplatin-based CT and ICIs resulted in a similar incidence of AKI and eGFR decay, suggesting the safety of their cautious use, even in CKD patients.

Long Non-Coding RNAs as Novel Biomarkers in the Clinical Management of Papillary Renal Cell Carcinoma Patients: A Promise or a Pledge?

Papillary renal cell carcinoma (pRCC) represents the second most common subtype of renal cell carcinoma, following clear cell carcinoma and accounting for 10-15% of cases. For around 20 years, pRCCs have been classified according to their mere histopathologic appearance, unsupported by genetic and molecular evidence, with an unmet need for clinically relevant classification. Moreover, patients with non-clear cell renal cell carcinomas have been seldom included in large clinical trials; therefore, the therapeutic landscape is less defined than in the clear cell subtype. However, in the last decades, the evolving comprehension of pRCC molecular features has led to a growing use of target therapy and to better oncological outcomes. Nonetheless, a reliable molecular biomarker able to detect the aggressiveness of pRCC is not yet available in clinical practice. As a result, the pRCC correct prognosis remains cumbersome, and new biomarkers able to stratify patients upon risk of recurrence are strongly needed. Non-coding RNAs (ncRNAs) are functional elements which play critical roles in gene expression, at the epigenetic, transcriptional, and post-transcriptional levels. In the last decade, ncRNAs have gained importance as possible biomarkers for several types of diseases, especially in the cancer universe. In this review, we analyzed the role of long non-coding RNAs (lncRNAs) in the prognosis of pRCC, with a particular focus on their networking. In fact, in the competing endogenous RNA hypothesis, lncRNAs can bind miRNAs, resulting in the modulation of the mRNA levels targeted by the sponged miRNA, leading to additional regulation of the target gene expression and increasing complexity in the biological processes.

MicroRNA Signatures in the Upper Urinary Tract Urothelial Carcinoma Scenario: Ready for the Game Changer?

Upper urinary tract urothelial carcinoma (UTUC) represents a minor subgroup of malignancies arising in the urothelium of the renal pelvis or ureter. The estimated annual incidence is around 2 cases per 100,000 people, with a mean age at diagnosis of 73 years. UTUC is more frequently diagnosed in an invasive or metastatic stage. However, even though the incidence of UTUC is not high, UTUC tends to be aggressive and rapidly progressing with a poor prognosis in some patients. A significant challenge in UTUC is ensuring accurate and timely diagnosis, which is complicated by the non-specific nature of symptoms seen at the onset of disease. Moreover, there is a lack of biomarkers capable of identifying the early presence of the malignancy and guide-tailored medical treatment. However, the growing understanding of the molecular biology underlying UTUC has led to the discovery of promising new biomarkers. Among these biomarkers, there is a class of small non-coding RNA biomarkers known as microRNAs (miRNAs) that are particularly promising. In this review, we will analyze the main characteristics of UTUC and focus on microRNAs as possible novel tools that could enter clinical practice in order to optimize the current diagnostic and prognostic algorithm.

Renal Oncocytoma: The Diagnostic Challenge to Unmask the Double of Renal Cancer.

Renal oncocytoma represents the most common type of benign neoplasm that is an increasing concern for urologists, oncologists, and nephrologists due to its difficult differential diagnosis and frequent overtreatment. It displays a variable neoplastic parenchymal and stromal architecture, and the defining cellular element is a large polygonal, granular, eosinophilic, mitochondria-rich cell known as an oncocyte. The real challenge in the oncocytoma treatment algorithm is related to the misdiagnosis due to its resemblance, at an initial radiological assessment, to malignant renal cancers with a completely different prognosis and medical treatment. Unfortunately, percutaneous renal biopsy is not frequently performed due to the possible side effects related to the procedure. Therefore, the majority of oncocytoma are diagnosed after the surgical operation via partial or radical nephrectomy. For this reason, new reliable strategies to solve this issue are needed. In our review, we will discuss the clinical implications of renal oncocytoma in daily clinical practice with a particular focus on the medical diagnosis and treatment and on the potential of novel promising molecular biomarkers such as circulating microRNAs to distinguish between a benign and a malignant lesion.