Percentage Of Renal Cell Carcinoma Research Articles

AXL targeting by a specific small molecule or monoclonal antibody inhibits renal cell carcinoma progression in an orthotopic mice model.

AXL tyrosine kinase activation enhances cancer cell survival, migration, invasiveness, and promotes drug resistance. AXL overexpression is typically detected in a high percentage of renal cell carcinomas (RCCs) and is strongly associated with poor prognosis. Therefore, AXL inhibition represents an attractive treatment option in these cancers. In this preclinical study, we investigated the antitumor role of a highly selective small molecule AXL inhibitor bemcentinib (BGB324, BerGenBio), and a newly developed humanized anti‐AXL monoclonal function blocking antibody tilvestamab, (BGB149, BerGenBio), in vitro and an orthotopic RCC mice model. The 786‐0‐Luc human RCC cells showed high AXL expression. Both bemcentinib and tilvestamab significantly inhibited AXL activation induced by Gas6 stimulation in vitro. Furthermore, tilvestamab inhibited the downstream AKT phosphorylation in these cells. The 786‐0‐Luc human RCC cells generated tumors with high Ki67 and vimentin expression upon orthotopic implantation in athymic BALB/c nude mice. Most importantly, both bemcentinib and tilvestamab inhibited the progression of tumors induced by the orthotopically implanted 786‐0 RCC cells. Remarkably, their in vivo antitumor effectiveness was not significantly enhanced by concomitant administration of a multi‐target tyrosine kinase inhibitor. Bemcentinib and tilvestamab qualify as compounds of potentially high clinical interest in AXL overexpressing RCC.

EARLY AND LATE POSTOPERATIVE COMPLICATIONS IN PATIENTS WITH LOCALIZED AND LOCALLY ADVANCED RENAL CELL CARCINOMA

Background: Modern Russian statistics show that the percentage of renal cell carcinoma (RCC) among all oncological diseases has increased and amounted to almost 5% in 2019. The main method of treating RCC is radical nephrectomy in localized RCC, which is supplemented by the removal of regional lymph nodes in locally advanced RCC. Aim: To evaluate early and late postoperative complications in patients with localized and locally advanced renal cell carcinoma. Methods: We’ve analyzed the results of surgical treatment and postoperative complications in 378 patients with clinically proven localized and locally developed RCC. Results: The total number of complications after surgical treatment of patients with localized and locally advanced RCC was 24 (6.3%) patients. Moreover, in the treatment of the localized form of RCC, postoperative complications are 3 times less common than in the locally advanced form of RCC (p <0.05). The most common complication after surgical treatment of RCC was bleeding which we observed in 11(2.9%) patients. Conclusion: After surgical treatment of RCC, the proportion of complications is not high, but they can have unpleasant consequences. In the late postoperative period the most common complication bleeding is followed by lymphorrhea and urinary tract infections.

UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination.

p53 is the most intensively studied tumour suppressor1. The regulation of p53 homeostasis is essential for its tumour-suppressive function2,3. Although p53 is regulated by an array of post-translational modifications, both during normal homeostasis and in stress-induced responses2-4, how p53 maintains its homeostasis remains unclear. UFMylation is a recently identified ubiquitin-like modification with essential biological functions5-7. Deficiency in this modification leads to embryonic lethality in mice and disease in humans8-12. Here, we report that p53 can be covalently modified by UFM1 and that this modification stabilizes p53 by antagonizing its ubiquitination and proteasome degradation. Mechanistically, UFL1, the UFM1 ligase6, competes with MDM2 to bind to p53 for its stabilization. Depletion of UFL1 or DDRGK1, the critical regulator of UFMylation6,13, decreases p53 stability and in turn promotes cell growth and tumour formation in vivo. Clinically, UFL1 and DDRGK1 expression are downregulated and positively correlated with levels of p53 in a high percentage of renal cell carcinomas. Our results identify UFMylation as a crucial post-translational modification for maintenance of p53 stability and tumour-suppressive function, and point to UFMylation as a promising therapeutic target in cancer.

Frequency of Angiomyolipomas Among Echogenic Nonshadowing Renal Masses (> 4 mm) Found at Ultrasound and the Utility of MRI for Diagnosis.

The purpose of this study is to evaluate what percentage of echogenic nonshadowing renal lesions larger than 4 mm found at ultrasound are angiomyolipomas (AMLs) and to review how to diagnose AMLs, with particular emphasis on the increasing role played by MRI. The study data were obtained at a single institution over a period of 45 months. Although some patients were being reviewed for specific symptoms, such as hematuria, pain, or recurrent urinary tract infections, most of the findings were incidental. Follow-up data on 158 lesions in 132 patients were available. Confirmation of diagnosis was made with follow-up imaging or with histopathologic examination. Ninety-eight (62.0%) of the lesions were AMLs, eight (5.1%) were renal cell carcinomas, three (1.9%) were oncocytomas, 17 (10.8%) were artifacts, seven (4.4%) were fat, five (3.2%) were calculi, another eight (5.1%) were scars, and 12 (7.6%) were complicated cysts. The mean age of patients with AML was significantly lower than that of patients without AML (61.71 [SD, 13.25] years vs 68.80 [SD, 17.85] years; p = 0.005). There was a female association with AMLs (p < 0.001). Echogenic nonshadowing renal lesions larger than 4 mm seen at ultrasound should not be assumed to represent an AML without follow-up because a percentage of renal cell carcinomas will be missed. Although certain ultrasound features can be useful in differentiating an AML from a renal cell carcinoma and CT is frequently diagnostic, an understanding of MRI is important because it can potentially detect lipid-poor AMLs.

Structure/Function Analysis of Recurrent Mutations in SETD2 Protein Reveals a Critical and Conserved Role for a SET Domain Residue in Maintaining Protein Stability and Histone H3 Lys-36 Trimethylation

The yeast Set2 histone methyltransferase is a critical enzyme that plays a number of key roles in gene transcription and DNA repair. Recently, the human homologue, SETD2, was found to be recurrently mutated in a significant percentage of renal cell carcinomas, raising the possibility that the activity of SETD2 is tumor-suppressive. Using budding yeast and human cell line model systems, we examined the functional significance of two evolutionarily conserved residues in SETD2 that are recurrently mutated in human cancers. Whereas one of these mutations (R2510H), located in the Set2 Rpb1 interaction domain, did not result in an observable defect in SETD2 enzymatic function, a second mutation in the catalytic domain of this enzyme (R1625C) resulted in a complete loss of histone H3 Lys-36 trimethylation (H3K36me3). This mutant showed unchanged thermal stability as compared with the wild type protein but diminished binding to the histone H3 tail. Surprisingly, mutation of the conserved residue in Set2 (R195C) similarly resulted in a complete loss of H3K36me3 but did not affect dimethylated histone H3 Lys-36 (H3K36me2) or functions associated with H3K36me2 in yeast. Collectively, these data imply a critical role for Arg-1625 in maintaining the protein interaction with H3 and specific H3K36me3 function of this enzyme, which is conserved from yeast to humans. They also may provide a refined biochemical explanation for how H3K36me3 loss leads to genomic instability and cancer.

Percentage of high‐grade carcinoma as a prognostic indicator in patients with renal cell carcinoma

The prognostic value of Fuhrman nuclear grade for patients with renal cell carcinoma has been well-characterized. However, to the authors' knowledge, the prognostic significance of the amount of high-grade renal cell carcinoma has not been previously analyzed. The authors identified 898 consecutive renal cell carcinoma cases treated with nephrectomy between 1989 and 2003. Histopathologic features that were captured based on re-review of all slides included histologic type, pathologic stage, conventional Fuhrman grade, and percentage of Fuhrman grade 3 and 4 carcinoma, as ascertained by visual inspection of histologic slides. The clinical endpoints were metastasis-free survival, cancer-specific survival, and overall survival. Kaplan-Meier analysis demonstrated that both conventional Fuhrman grading and the percentage of Fuhrman grade 3 and 4 carcinoma were highly correlated with all 3 measures of patient survival (P < .0001). The creation of 3 categories of the percentage of Fuhrman grade 3 and 4 carcinoma (0%, 1-50%, and 51-100%) generated distinctly separate survival curves. On Cox proportional hazards multivariate analysis, TNM stage, tumor size, and the percentage of Fuhrman grade 3 and 4 carcinoma were all found to be significantly associated with all 3 types of patient survival (all P values <.05). The determination of the percentage of renal cell carcinoma that is 0%, 1% to 50%, or 51% to 100% high Fuhrman grade 3 and 4 is a simple and powerful measurement of patient outcome after surgery that provides additional prognostic information beyond stage, tumor size, and conventional Fuhrman grade. This prognostic information could be useful in the stratification of patients into prognostic groups for the development of more individualized follow-upschedules and for enrollment into clinical trials.

Estudio clínico-patológico de los adenocarcinomas renales incidentales

To determine the percentage of renal cell carcinomas incidentally diagnosed (IRCC) and to compare their clinical and pathological characteristics with symptomatic or non-incidentally diagnosed tumors (SRCC). We retrospectively study 189 patients who were diagnosed of renal carcinoma between 1990 and 1999. 166 underwent surgery (149 radical nephrectomy; 17 nephron-sparing surgery). We determine the percentage of IRCC detected by radiological tests and compare them with the SRCC diagnosed after presenting with some of the classic symptoms or metastasis, with special focus on tumor size, pathology stage, tumor recurrence, progression and evolution. 87 SRCC (46%); 102 SRCC (54%). There are not differences in terms of age, gender, side, and postoperative hospital stay. Tumor size was higher in the SRCC (mean 8.5 cm) than in the IRCC (6.3 cm). SRCC tumor stage was: pT1 27.3%, pT2 27.3%, pT3a 23.8%, pT3b 16.6%, pT3c 2.3%, and pT4 2.3%; IRCC stage was: pT1 51.3%, pT2 25.6%, pT3a 10.9%, pT3b 10.9%, pT3c 1.2%, and no pT4. The percentage of patients with lymph node involvement was higher (p = 0.02) in the SRCC (15%) than in the IRCC (4.8%). The percentage of patients with metastasis at the time of diagnosis was higher in the SRCC group (26%) than in the IRCC (9.2%). Recurrences were more frequent in the SRCC Group (8.3%) than in the IRCC (1.2%) (p = 0.07). Tumor progression was more frequent in the SRCC group (34%) than in the IRCC (7.3%) (p<0.01). 76% of the patients undergoing nephron sparing surgery were IRCC. Currently, there is a high percentage of IRCC (46% in our series from 1990-99). Renal tumors presenting as IRCC have better prognosis, since they have significantly smaller size, lower stage, less advanced disease, less recurrences, and less progression than SRCC.

Prognostic significance of the mode of detection in renal tumours.

To evaluate the mode of detection of 400 renal tumours as a prognostic factor compared with the usual clinical and pathological prognostic variables. The data were reviewed for 400 patients operated for a renal tumour at our institution between 1984 and 1999, analysing the prognostic value of age, sex, tumour size, stage, grade, vein invasion, adrenal gland invasion, lymph node invasion, metastasis, and mode of detection (incidental or not). The survival rates were assessed using the Kaplan-Meier method and log-rank test, and the data evaluated using multivariate analysis with the Cox proportional-hazard model. In all, 151 (38%) renal tumours were discovered incidentally. There was no significant difference in the percentage of renal cell carcinoma found between the groups of patients discovered incidentally or not (94.4% vs 93.9%). Tumours were smaller in the incidental group (5.7 cm vs 8.7 cm, P < 0.001). In the incidental group, 15.2% of the tumours were treated with partial nephrectomy, against 1.2% in the symptomatic group (P < 0.001). The specific survival was significantly better in patients with renal tumours discovered incidentally (log-rank test, P < 0.001). The multivariate analysis showed that the mode of detection, stage, grade, metastasis (all P < 0.001), and lymphatic extension (P = 0.005) were independent prognostic factors. The incidental discovery of renal tumours gives a supplementary benefit to patients in terms of survival, and should be considered as a prognostic factor in addition to stage and grade.

Analysis of histological heterogeneity in renal cell carcinoma: tumor size-related histological change and its prognostic significance.

It is well recognized that the histology of renal cell carcinoma (RCC) is often heterogeneous. It is also believed that the prognosis of patients with large tumors is generally poorer than those with small tumors. However, there has been no detailed study on changes in histological features of RCCs associated with tumor growth. This study was conducted to investigate whether there are any specific histological changes related to tumor size and to study the prognostic value of histological parameters in RCCs. The presence or absence of each histological component (3 cell types and 5 histological architectures) was investigated in 110 RCCs. The tumor size-associated changes in the histological composition of the RCCs were evaluated, and the prognostic significance of the histological parameters was analyzed using univariate and multivariate analysis. The percentage of RCCs with multiple cell types increased with tumor size, whereas increases in multiplicity were not as prominent in the histological architectures. Several characteristic changes, however, were observed in both cell types and architectures. RCCs with a pure clear cell, pure alveolar pattern or cystic architectural pattern decreased, while those with granular or spindle/pleomorphic cell types, or papillary or solid architectural patterns increased with tumor size. A univariate analysis revealed that a clear cell type and an alveolar or cystic architectural pattern were associated with a better prognosis, while spindle/pleomorphic cells and a solid architecture pattern correlated with a poorer prognosis. Multivariate analysis of cell types and architectures showed, however, that only the presence of spindle/pleomorphic cell types and a solid architecture were independent prognostic variables. The histological composition of RCCs varied according to the size of the tumor. Sarcomatous components increased with tumor size and were independently associated with a poor prognosis. Further study is warranted to correlate specific genetic alterations with tumor growth-related histological changes in RCCs.

Renal cell carcinoma and osseous metastases. Case report and literature review

Renal cell carcinoma is one of the great mimics in medicine. The diagnosis is complicated by clinical presentations involving a multitude of symptoms, often associated with the sites of metastasis. A high percentage of renal cell carcinomas have metastasized at the time of initial presentation, and symptoms associated with this metastasis may actually initiate the diagnosis. Because the site of tumor origin is frequently unknown, a diagnostic strategy for identifying the primary source has been proposed. The prognosis for renal cell carcinoma with metastasis is poor, with fewer than 9% of patients surviving at 5 years. Consequently, treatment is directed primarily at palliation of painful symptoms and stabilization of bony structures. With these goals in mind, treatment modalities run the gamut from radiotherapy, to curettage with polymethyl methacrylate augmentation, to amputation. In the case reported here, renal cell carcinoma was diagnosed in the course of evaluation of a painful lytic lesion of the foot. Treatment alternatives and associated risks and complications were discussed at some length and the patient chose curettage and packing with polymethyl methacrylate in combination with radiotherapy. This approach was successful in palliation of pain and maintenance of walking ability and independence.