Clinicopathologic features and prognostic factors in patients with renal cell carcinoma with sarcomatoid differentiation

Zhao, Yuan; Chen, Hong; Xie, Yao; Zhang, Chuanhong; Hou, Yirui; Jin, Mulan

doi:10.1111/apm.13035

Cited by 12 publications

(20 citation statements)

References 29 publications

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“…With the approximate 270,000 new cases worldwide per year, renal cell carcinoma (RCC) represents 2 to 3% of all adult malignant tumors and ascends to the most common genitourinary cancer [1]. Based on the various molecular genetic features, RCC was identified as different histopathologic classifications, of which clear cell renal cell carcinoma (ccRCC) comprised the main histopathologic subtype, accounting for 70 to 80% of RCC [2].…”

Section: Introductionmentioning

confidence: 99%

Bioinformatics profiling integrating a three immune-related long non-coding RNA signature as a prognostic model for clear cell renal cell carcinoma

et al. 2020

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Background: Renal cell carcinoma (RCC) is one of the most common aggressive malignant tumors in urogenital system, and the clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinoma. Immune related long non-coding RNAs (IRlncRs) plentiful in immune cells and immune microenvironment (IME) are potential in evaluating prognosis and assessing the effects of immunotherapy. A completed and meaningful IRlncRs analysis based on abundant ccRCC gene samples from The Cancer Genome Atlas (TCGA) will provide insight in this field. Methods: Based on the TCGA dataset, we integrated the expression profiles of IRlncRs and overall survival (OS) in the 611 ccRCC patients. The immune score of each sample was calculated based on the expression level of immunerelated genes and used to identify the most meaningful IRlncRs. Survival-related IRlncRs (sIRlncRs) was estimated by calculating the algorithm of difference and COX regression analysis in ccRCC patients. Based on the median immune-related risk score (IRRS) developed from the screened sIRlncRs, the high-risk and low-risk components were distinguished. Functional annotation was detected by gene set enrichment analysis (GSEA) and principal component analysis (PCA), and the immune composition and purity of the tumor was evaluated by microenvironment cell population records. The expression levels of three sIRlncRs were verified in various tissues and cell lines. Results: A total of 39 IRlncRs were collected by Pearson correlation analyses among immune score and the lncRNA expression. A total of 7 sIRlncRs were significantly associated with the clinical outcomes of ccRCC patients. Three sIRl-ncRs (ATP1A1-AS1, IL10RB-DT and MELTF-AS1) with the most significant prognostic values were enrolled to build the IRRS model in which the OS of in the high-risk group was shorter than that in the low-risk group. The IRRS was identified as an independent prognosis factor and correlated with the OS. The high-risk group and low-risk group illustrated different distributions in PCA and different immune status in GSEA. Besides, we found the more significant expression in certain ccRCC cell lines and tumor tissues of ccRCC patients compared with the HK-2 and adjacent tissues respectively. Additionally, the expression levels of lncR-MELTF-AS1 and IL10RB-DT were remarkably enhanced along the more advanced T-stages, but the lncR-ATP1A1-AS1 showed the inverse gradient.

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Section: Introductionmentioning

confidence: 99%

Bioinformatics profiling integrating a three immune-related long non-coding RNA signature as a prognostic model for clear cell renal cell carcinoma

et al. 2020

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“…Zhao et al examined 139 RCC patients and aimed to explore the relationship between clinical and pathologic features with prognostic factors and indicated that microvascular invasion was a significant predictor of prognosis (24). Bernardos et al retrospectively analyzed 153 pT3apN0cM0 kidney cancer patients and indicated that tumor necrosis and microvascular invasion were associated with tumor recurrence (25).…”

Section: Discussionmentioning

confidence: 99%

Arterial Spin Labeling MRI for Predicting Microvascular Invasion of T1 Staging Renal Clear Cell Carcinoma Preoperatively

et al. 2021

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BackgroundMicrovascular invasion (MVI) is a valuable factor for T1 staging renal clear cell carcinoma (ccRCC) operation strategy decision, which is confirmed histopathologically post-operation. This study aimed to prospectively evaluate the performance of arterial spin labeling (ASL) MRI for predicting MVI of T1 staging ccRCC preoperatively.Methods16 volunteers and 39 consecutive patients were enrolled. MRI examinations consisted of ASL (three post label delays separately) of the kidney, followed by T1 and T2-weighted imaging. Two sessions of ASL were used to evaluate the reproducibility on volunteers. Renal blood flow of renal cortex, medulla, the entire and solid part of the tumor were measured on ASL images. Conventional imaging features were extracted. MVI and WHO/ISUP classification were evaluated histopathologically. A paired t‐test was used to compare the renal cortex and medulla between ASL 1 and ASL 2. The reproducibility was assessed using the intraclass correlation. Differences in mean perfusion between the entire and the solid parts of tumors with or without MVI were assessed separately using Student’s t test. The diagnostic performance was assessed. Logistic regression analysis was used to indicate the independent prediction index for MVI.ResultsThe two sessions of ASL showed no significant difference between the mean cortex values of RBF. The cortical RBF measurements demonstrated good agreement. 12 ccRCCs presented with MVI histopathologically. Mean perfusion of the solid part of tumors with MVI were 536.4 ± 154.8 ml/min/100 g (PLD1), 2912.5 ± 939.3 ml/min/100 g (PLD2), 3280.3 ± 901.2 ml/min/100 g (PLD3). Mean perfusion of the solid part of tumors without MVI were 453.5 ± 87.2 ml/min/100 g (PLD1), 1043.6 ± 695.8 ml/min/100 g (PLD2), 1577.6 ± 1085.8 ml/min/100 g (PLD3). These two groups have significant difference at all the PLDs (p < 0.05). The RBF of PLD1 of the solid part of tumor perfusion showed well diagnostic performance for predicting MVI: sensitivity 75%, specificity 100%, positive predictive value 66.7%, and negative predictive value 95.7%. The maximum diameter of the tumor, ill-defined margin, and the solid part of tumor perfusion were the independent prediction index for MVI.ConclusionASL MR imaging has good reproducibility for renal cortex, and good diagnostic performance for predicting MVI for ccRCC.

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“…It was reported that patients with sarcomatoid carcinoma have a poorer prognosis than classical ccRCC [8,26], therefore uncovering the genomic characterization of sarcomatoid transformation in ccRCC is vital. The most altered pathways of sarcomatoid RCC (sRCC) involved VHL (72%), chromatin remodeling genes (72%), MTOR pathway (50%), DNA repair (30%), and the Hippo-YAP pathway (20%) [27].…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological and Genomic Analysis of a Chinese ccRCC Patient with Multiple Morphologies and Rapid Progression : A Case Report

Yang

Wang

Liang

et al. 2020

Preprint

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Background: Renal cell carcinoma (RCC) with sarcomatoid differentiation and multiple metastases is highly aggressive RCC with poor prognosis. However, there are not sufficient report on the genetic alterations and tumor immune microenviroment (TIME) of RCC with complex pathological morphology and aggressive behavior.Case presentation: A rare Chinese RCC case with complex pathological morphology and multiple subcutaneous and soft tissue metastases was reported. The clinical manifestations, histomorphology, immunophenotype and follow-up data were collected and analyzed. We performed target region sequencing and immunohistochemistry staining in different morphological regions of the primary tumor and the peritoneal metastasis. Microscopically, this primary tumor was composed of three different histological variations, including ccRCC like region, eosinophilic papillary structure and sarcomatoid differentiation. The peritoneal metastasis partially showed rhabdoid differentiation. IHC staining didn’t display positivity for characteristic markers. IHC for inflammatory cells showed that CD8+T cells and tumor associated neutrophils (TANs) were significantly increased in the sarcomatous areas and peritoneal metastatic tumor. Genomic analysis indicated that VHL mutations were present in all types of pathological regions and peritoneal metastatic tumor. Therefore, the pathological diagnosis of high-grade ccRCC with sarcomatoid differentiation was established. Additionally, we also found SETD2, TP53 and PDGFRA mutations were observed in sarcomatoid tumor area, whereas BRCA2, ATR, CYLD, YAP1 and COL5A3 mutations were specifically detected in peritoneal metastases. These findings are rather striking because some genes e.g., ATR serine/threonine kinase (ATR) and Hippo signaling (YAP1), PI3K-Akt signaling (PDGFRA) and T cell receptor signaling (COL5A3) were previously reported to be very rare in ccRCC patients.Conclusions: Using next-generation sequencing and TIME analysis, multiple low-frequency mutant genes including PDGFRA, ATR, YAP1 and COL5A3 and increased CD8+ T cells and neutrophils were detected in this rare Chinese ccRCC. These findings potentially provide new evidence and molecular markers for accurately assessing the biological behavior of ccRCC.

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Clinicopathologic features and prognostic factors in patients with renal cell carcinoma with sarcomatoid differentiation

Cited by 12 publications

References 29 publications

Bioinformatics profiling integrating a three immune-related long non-coding RNA signature as a prognostic model for clear cell renal cell carcinoma

Bioinformatics profiling integrating a three immune-related long non-coding RNA signature as a prognostic model for clear cell renal cell carcinoma

Arterial Spin Labeling MRI for Predicting Microvascular Invasion of T1 Staging Renal Clear Cell Carcinoma Preoperatively

Clinicopathological and Genomic Analysis of a Chinese ccRCC Patient with Multiple Morphologies and Rapid Progression : A Case Report

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