Pulmonary metastasectomy in renal cell carcinoma: Predictive and prognostic elements from paired histopathological analysis of primary tumors and respective metastases

2021 ◽  
pp. 239936932110285
Author(s):  
Melissa Bersanelli ◽  
Sebastiano Buti ◽  
Letizia Gnetti ◽  
Elena Varotti ◽  
Paolo Carbognani ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Prognostic Value ◽  
Positive Impact ◽  
Left Lung ◽  
Pulmonary Metastasectomy ◽  
Histopathological Analysis ◽  
Primary Tumors ◽  
Paired Samples

Objective: To identify histopathological and immunophenotypical features with potential predictive or prognostic value in patients undergoing pulmonary metastasectomy from renal cell carcinoma (RCC). Methods: We retrospectively collected all consecutive patients undergoing pulmonary metastasectomy from RCC after prior nephrectomy. Paired samples of primary tumors and corresponding pulmonary metastases were analyzed, revising histopathological features and testing C-MET, mTOR, and PD-L1 by immunohistochemistry. Results: A total of 25 patients were included. Median overall survival (mOS) from metastasectomy was 5.5 years (95% CI = 1.9–9.1). The laterality of metastases had a significant predictive value, with median relapse-free survival (mRFS) from metastasectomy not reached (NR) at mean follow-up (FU) of 60.8 months for left lung involvement, mRFS of 52.9 months (95% CI = 0–145.5) for the right lung and 6.4 months (95% CI = 1.7–11) for bilateral metastases ( p = 0.028). Primary RCC with positive expression of mTOR had higher mOS after metastasectomy than negative cases ( p < 0.001), NR at mean FU of 4.3 years versus mOS of 2 years (95% CI = 0.7–3.3), respectively. PD-L1 positivity on intra-tumor (TILs) and peri-tumor (RILs) infiltrating lymphocytes of metastases was related to higher OS, NR versus 2 years (95% CI = 1.2–2.7, p = 0.003), and NR versus 1.4 years (95% CI = 0.2–2.6, p = 0.012), respectively. The shorter was the surgical interval, the more probably the metastases had high c-MET expression (>70%) ( p = 0.007) and PD-L1 expression >10% on TILs ( p = 0.024). Conclusions: mTOR positivity on primary RCC could be a favorable prognostic factor to select patients for pulmonary metastasectomy. The positive impact of PD-L1 expression on immune cells is opposite to the well-known negative prognostic value of PD-L1 on tumor cells in RCC.

1757: The Prognostic Value of Histologic Subtypes in Renal cell Carcinoma (RCC). A Multicenter Experience in 4063 Patients

2004 ◽  
Vol 171 (4S) ◽  
pp. 464-465 ◽  
Author(s):  
Jean-Jacques Patard ◽  
Nathalie Rioux-Leclercq ◽  
Luca Cindolo ◽  
Vincenzo Ficarra ◽  
Ken Han ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Prognostic Value ◽  
Histologic Subtypes

scholarly journals Quantitative 3-tesla multiparametric MRI in differentiation between renal cell carcinoma subtypes

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Ali Elsorougy ◽  
Hashim Farg ◽  
Dalia Bayoumi ◽  
Mohamed Abou El-Ghar ◽  
Magda Shady
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Multiparametric Mri ◽  
Histopathological Analysis ◽  
Adc Value ◽  
Intensity Index ◽  
Apparent Diffusion ◽  
The Mean

Abstract Background MRI provides several distinct quantitative parameters that may better differentiate renal cell carcinoma (RCC) subtypes. The purpose of the study is to evaluate the diagnostic accuracy of apparent diffusion coefficient (ADC), chemical shift signal intensity index (SII), and contrast enhancement in differentiation between different subtypes of renal cell carcinoma. Results There were 63 RCC as regard surgical histopathological analysis: 43 clear cell (ccRCC), 12 papillary (pRCC), and 8 chromophobe (cbRCC). The mean ADC ratio for ccRCC (0.75 ± 0.13) was significantly higher than that of pRCC (0.46 ± 0.12, P < 0.001) and cbRCC (0.41 ± 0.15, P < 0.001). The mean ADC value for ccRCC (1.56 ± 0.27 × 10−3 mm2/s) was significantly higher than that of pRCC (0.96 ± 0.25 × 10−3 mm2/s, P < 0.001) and cbRCC (0.89 ± 0.29 × 10−3 mm2/s, P < 0.001). The mean SII of pRCC (1.49 ± 0.04) was significantly higher than that of ccRCC (0.93 ± 0.01, P < 0.001) and cbRCC (1.01 ± 0.16, P < 0.001). The ccRCC absolute corticomedullary enhancement (196.7 ± 81.6) was significantly greater than that of cbRCC (177.8 ± 77.7, P < 0.001) and pRCC (164.3 ± 84.6, P < 0.001). Conclusion Our study demonstrated that multiparametric MRI is able to afford some quantitative features such as ADC ratio, SII, and absolute corticomedullary enhancement which can be used to accurately distinguish different subtypes of renal cell carcinoma.

scholarly journals Prognostic Value of Plasma hPG80 (Circulating Progastrin) in Metastatic Renal Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 375
Author(s):  
Manish Kohli ◽  
Winston Tan ◽  
Bérengère Vire ◽  
Pierre Liaud ◽  
Mélina Blairvacq ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Prognostic Value ◽  
Risk Model ◽  
Predictive Accuracy ◽  
Area Under The Curve ◽  
Risk Groups ◽  
Prognostic Impact ◽  
Significant Difference

Precise management of kidney cancer requires the identification of prognostic factors. hPG80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including renal cell carcinoma (RCC). In this study, we evaluated the prognostic value of plasma hPG80 in 143 prospectively collected patients with metastatic RCC (mRCC). The prognostic impact of hPG80 levels on overall survival (OS) in mRCC patients after controlling for hPG80 levels in non-cancer age matched controls was determined and compared to the International Metastatic Database Consortium (IMDC) risk model (good, intermediate, poor). ROC curves were used to evaluate the diagnostic accuracy of hPG80 using the area under the curve (AUC). Our results showed that plasma hPG80 was detected in 94% of mRCC patients. hPG80 levels displayed high predictive accuracy with an AUC of 0.93 and 0.84 when compared to 18–25 year old controls and 50–80 year old controls, respectively. mRCC patients with high hPG80 levels (>4.5 pM) had significantly lower OS compared to patients with low hPG80 levels (<4.5 pM) (12 versus 31.2 months, respectively; p = 0.0031). Adding hPG80 levels (score of 1 for patients having hPG80 levels > 4.5 pM) to the six variables of the IMDC risk model showed a greater and significant difference in OS between the newly defined good-, intermediate- and poor-risk groups (p = 0.0003 compared to p = 0.0076). Finally, when patients with IMDC intermediate-risk group were further divided into two groups based on hPG80 levels within these subgroups, increased OS were observed in patients with low hPG80 levels (<4.5 pM). In conclusion, our data suggest that hPG80 could be used for prognosticating survival in mRCC alone or integrated to the IMDC score (by adding a variable to the IMDC score or by substratifying the IMDC risk groups), be a prognostic biomarker in mRCC patients.

scholarly journals Hyperprogressive disease after radiotherapy combined with anti-PD-1 therapy in renal cell carcinoma: a case report and review of the literature

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chao Liu ◽  
Jingjing Piao ◽  
Zhiyang Shang
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
General Condition ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Lung Metastases ◽  
Left Lung ◽  
The Third ◽  
Bidirectional Regulation ◽  
Hyperprogressive Disease

Abstract Background Studies have shown that immune checkpoint inhibitors (ICIs) have limited efficacy and can even increase tumour burden in short time periods. This is usually called hyperprogressive disease (HPD). To date, there are few reports regarding HPD; fewer have analysed the relationship between HPD and radiotherapy combined with ICIs, and their conclusions are controversial. Case presentation A 42-year-old woman was diagnosed with stage IV renal clear cell carcinoma. The patient had previously received sorafenib and pazopanib as first- and second-line therapies, respectively. She received radiotherapy combined with nivolumab. Eighteen days after administration of the third dose of nivolumab, the patient’s general condition deteriorated; this was associated with immune-related adverse events. Computed tomography showed that the diameter of left lung metastases had sharply increased. A biopsy of the lung metastasis showed no infiltration of lymphocytes. The patient’s general condition worsened and she died of the disease on the 70th day after administration of the third dose of nivolumab. Conclusions This report describes the development of HPD following the administration of radiotherapy combined with ICIs in a case of advanced renal cell carcinoma. The case indicates that radiotherapy may show bidirectional regulation effects on anti-tumour immune response. If the immunosuppressive function of radiotherapy is dominant, combined with ICIs, it could result in HPD.

scholarly journals MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Brian Shuch ◽  
Ryan Falbo ◽  
Fabio Parisi ◽  
Adebowale Adeniran ◽  
Yuval Kluger ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Predictive Biomarkers ◽  
Cell Renal Cell Carcinoma ◽  
Primary Tumors ◽  
Distant Tissue ◽  
Significant Expression ◽  
Metastatic Sites

Aims. Inhibitors of the MET pathway hold promise in the treatment for metastatic kidney cancer. Assessment of predictive biomarkers may be necessary for appropriate patient selection. Understanding MET expression in metastases and the correlation to the primary site is important, as distant tissue is not always available.Methods and Results. MET immunofluorescence was performed using automated quantitative analysis and a tissue microarray containing matched nephrectomy and distant metastatic sites from 34 patients with clear cell renal cell carcinoma. Correlations between MET expressions in matched primary and metastatic sites and the extent of heterogeneity were calculated. The mean expression of MET was not significantly different between primary tumors when compared to metastases (P=0.1). MET expression weakly correlated between primary and matched metastatic sites (R=0.5) and a number of cases exhibited very high levels of discordance between these tumors. Heterogeneity within nephrectomy specimens compared to the paired metastatic tissues was not significantly different (P=0.39).Conclusions. We found that MET expression is not significantly different in primary tumors than metastatic sites and only weakly correlates between matched sites. Moderate concordance of MET expression and significant expression heterogeneity may be a barrier to the development of predictive biomarkers using MET targeting agents.

Prognostic value of carbonic anhydrase IX and HIF-1α in renal cell carcinoma

2012 ◽  
Vol 38 (1) ◽  
pp. 1-7
Author(s):  
Bilal Gunaydin ◽  
Asif Yildirim ◽  
Ebru Zemheri ◽  
Seyma Ozkanli ◽  
Serhat Gocer ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Carbonic Anhydrase ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Prognostic Value ◽  
Carbonic Anhydrase Ix

Diagnostic ability of four cell-free miRNA signatures pre- and post-nephrectomy concordantly found in the tumor and blood from patients with renal cell carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16577-e16577
Author(s):  
Matias Bustos ◽  
Rebecca Gross ◽  
Rebeka Dejenie ◽  
Ryu Suyeon ◽  
Negin Rahimzadeh ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Renal Cell ◽  
Incidental Finding ◽  
Area Under The Curve ◽  
Roc Curves ◽  
Diagnostic Ability ◽  
Paired Samples ◽  
Tumor Tissues

e16577 Background: Renal cell carcinoma (RCC) has shown an increase in incidence based on continued incidental finding of these tumors by imaging. There is a need for reliable biomarkers like MicroRNAs (miRNA) that are released by the tumor cells and can be detected in assays using blood or urine samples. The first aim of the present pilot study is to determine the diagnostic ability of cell-free miRNA (cfmiR) biomarkers released by RCC tumor cells in urine and plasma samples. The secondary aim was to determine cfmiRs utility in monitoring RCC before and after radical or partial nephrectomy. Methods: We profiled tumor tissues (n = 11), pre-operative (pre-P n = 18; pre-U n = 17) and post-operative (post-P n = 18; post-U n = 17) plasma and urine paired samples from 18 RCC patients with a median follow-up of 18.4 months. As a control, we utilized plasma (n = 73) and urine (n = 16) samples taken from normal healthy donors (NHD). All specimens (n = 170) were processed and analyzed using HTG EdgeSeq miRNA whole transcriptome assay. All of the samples were normalized and DESeq2. Only miRNAs with a FC < -1.5 or > 1.5, FDR < 0.05, normalized counts > 30 were considered Results: We assessed urine, plasma, and tissue for 2083 miRNAs. The pre-U profiles from patients with RCC and NHD were compared to find differentially expressed (DE) cfmiRs. We found 182 cfmiRs DE in pre-U RCC, of which 106 were upregulated and 76 were downregulated. Similarly, we found 830 cfmiRs DE in the pre-P from RCC compared to NHD, of which 192 were upregulated and 638 were downregulated. We then searched for the top 100 miRNAs most frequently detected and identified in the tumor and in pre-P and pre-U samples. Forty miRNAs were consistently found and highly detected in all of the specimens. Of those 40 miRNAs, 33 cfmiRs were found DE in pre-P and 9 cfmiRs significantly decreased in post-P samples after surgery to the level values observed in the plasma from NHD. In the pre-P and pre-U samples from RCC patients, let-7a-5p, let-7b-5p, miR-23b-3p, and miR-30d-5p were found to be consistently upregulated compared to their respective controls. By using receiving operating characteristic (ROC) curves we assessed the area under the curve (AUC) of all the four cfmiRs in detecting RCC patients. The values of AUC for the four cfmiRs detected in pre-P ranged from 76.2-81% [sensitivity, 61.1-83.3%; specificity, 74-86.3%] and in pre-U samples ranged from 76.1-82.4% [sensitivity, 64.7-70.6%; specificity, 100%]. We observed that the four cfmiRs significantly decreased in the post-U samples from RCC patients after surgery to the level values observed in urine from NHD. Conclusions: Our results propose a four cfmiR signature as a potential diagnostic/monitoring urine biomarker that is also detectable in the plasma and tumor tissues from RRC. Further studies to validate these cfmiRNAs as biomarkers for RCC in blood and urine are ongoing.

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