GRIM‑19 deficiency promotes clear cell renal cell carcinoma progression and is associated with high TNM stage and Fuhrman grade

AbstractClear cell renal cell carcinoma (ccRCC) is the most frequent and aggressive subtype of renal carcinoma. So far, the basis of its oncogenesis remains unclear resulting in a deficiency of usable and reliable biomarkers for its clinical management. Previously, we showed that nuclear expression of the signal transducer and activator of transcription 3 (STAT3), phosphorylated at its serine 727 (pS727), was inversely proportional to the overall survival of ccRCC patients. Therefore, in the present study, we validated the value of pS727-STAT3 as a clinically relevant biomarker in ccRCC. This work is a retrospective study on 82 ccRCC patients treated with nephrectomy and followed-up for 10 years. Immunohistochemical expression of pS727-STAT3 was analyzed on a tissue microarray and nuclear and cytosolic levels were correlated with clinical outcome of patients. Our results showed that pS727-STAT3 levels, whether in the nucleus (p = 0.002; 95% CI 1.004–1.026) or the cytosol (p = 0.040; 95% CI 1.003–1.042), significantly correlate with patients’ survival in an independent-manner of clinicopathological features (Fuhrman grade, risk group, and tumor size). Moreover, we report that patients with high pS727-STAT3 levels who undergone adjuvant therapy exhibited a significant stabilization of the disease (~ 20 months), indicating that pS727-STAT3 can pinpoint a subset of patients susceptible to respond well to treatment. In summary, we demonstrated that high pS727-STAT3 levels (regardless of their cellular location) correlate with low overall survival of ccRCC patients, and we suggested the use of pS727-STAT3 as a prognostic biomarker to select patients for adjuvant treatment to increase their survival.

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Obstructive sleep apnea and Fuhrman grade in patients with clear cell renal cell carcinoma treated surgically

World Journal of Urology ◽

10.1007/s00345-016-1830-6 ◽

2016 ◽

Vol 35 (1) ◽

pp. 51-56 ◽

Cited By ~ 7

Author(s):

Antoni Vilaseca ◽

Daniel P. Nguyen ◽

Emily A. Vertosick ◽

Renato B. Corradi ◽

Mireia Musquera ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Fuhrman Grade ◽

Obstructive Sleep

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CT prediction of the Fuhrman grade of clear cell renal cell carcinoma (RCC): towards the development of computer-assisted diagnostic method

Abdominal Imaging ◽

10.1007/s00261-015-0531-8 ◽

2015 ◽

Vol 40 (8) ◽

pp. 3168-3174 ◽

Cited By ~ 21

Author(s):

Hannu Huhdanpaa ◽

Darryl Hwang ◽

Steven Cen ◽

Brian Quinn ◽

Megha Nayyar ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Diagnostic Method ◽

Clear Cell ◽

Computer Assisted ◽

Cell Renal Cell Carcinoma ◽

Fuhrman Grade

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Use of preoperative C-reactive protein to improve predictive accuracy in clear cell renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.474 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 474-474

Author(s):

Stephan Kruck ◽

Felix K. Chun ◽

Axel S. Merseburger ◽

Hossein Tezval ◽

Marcus Scharpf ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Predictive Accuracy ◽

Tnm Stage ◽

C Reactive Protein ◽

Cell Renal Cell Carcinoma ◽

Reactive Protein ◽

Karnofsky Index

474 Background: White blood cell count (WBC) and C-reactive protein (CRP) are reliable biomarkers in clear cell renal cell carcinoma (ccRCC). Nevertheless, accepted cut-offs values for risk stratifications are missing. This study re-evaluated the prognostic and predictive significance of preoperatively WBC and CRP that independently predicts patient prognosis and to determine optimal cut-off values for CRP. Methods: 327 patients with surgery for ccRCC were retrospectively evaluated from 1996 to 2005. Cox-proportional hazard models were used, adjusted for the effects of tumor stage, tumor size, Fuhrman grade, and Karnofsky-Index; and to evaluate the prognostic significance of WBC and CRP; and to identify cut-off values. Identified cut-offs were correlated with clinico-pathological parameters and used to estimate cancer-speciﬁc survival (CSS). To prove any additional predictive accuracy of the identified cut-off it was compared to a clinico-pathological base model using Harrell c-index. Results: In univariable analyses WBC was a significant prognostic marker at a concentration of 9.5/µl (HR: 1.83) and 11.0/µl (HR: 2.09) and supported a CRP value of 0.25 mg/dL (HR: 6.47, p < 0.001) and 0.5mg/dL (HR: 7.15, p < 0.001) as potential cut-off values. If adjusted by the multivariable models WBC showed no clear breakpoint, but a CRP-value of 0.25mg/dL (HR: 2.80, p = 0.027) proved to be optimal. Reduced CSS was proven for CRP 0.25 mg/dL (median: 69.9 vs. 92.3 months). Median follow-up was 57.5 months with 72 (22%) tumor related deaths. The final model built by the addition of CRP 0.25mg/dL did not improve predictive accuracy (c-index = 0.877) than compared to the clinico-pathological base model (c-index =0.881) which included TNM-stage, grading and Karnofsky-Index. Conclusions: Multivariable analyses revealed an optimal breakpoint of CRP at a value of 0.25mg/dL best to stratify patients at risk of cancer-specific mortality, but CRP 0.25mg/dL added no additional information in the prediction model. Therefore we cannot recommend to measure CRP as the traditional parameters of TNM-stage, grading and Karnofsky-Index were already of high predictive accuracy.

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Delayed enhancement of the peritumoural cortex in clear cell renal cell carcinoma: correlation with Fuhrman grade

Clinical Radiology ◽

10.1016/j.crad.2018.06.010 ◽

2018 ◽

Vol 73 (11) ◽

pp. 982.e1-982.e7 ◽

Cited By ~ 2

Author(s):

X. Zhang ◽

Y. Wang ◽

L. Yang ◽

T. Li ◽

J. Wu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Delayed Enhancement ◽

Cell Renal Cell Carcinoma ◽

Fuhrman Grade

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Standardized Uptake Values Highly Correlate with Tumor Size and Fuhrman Grade in Patients with Clear Cell Renal Cell Carcinoma

Asian Pacific Journal of Cancer Prevention ◽

10.7314/apjcp.2014.15.18.7821 ◽

2014 ◽

Vol 15 (18) ◽

pp. 7821-7824 ◽

Cited By ~ 9

Author(s):

Emre Can Polat ◽

Alper Otunctemur ◽

Emin Ozbek ◽

Huseyin Besiroglu ◽

Murat Dursun ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Tumor Size ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Fuhrman Grade ◽

Standardized Uptake Values

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Synchronous Brain Metastases as a Poor Prognosis Factor in Clear Cell Renal Carcinoma: A Strong Argument for Systematic Brain Screening

10.21203/rs.3.rs-196626/v1 ◽

2021 ◽

Author(s):

Valentine Ruste ◽

Marie-Pierre Sunyach ◽

Ronan Tanguy ◽

Emmanuel Jouanneau ◽

Camille Schiffler ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Whole Brain Radiotherapy ◽

Progression Free Survival ◽

Cell Renal Cell Carcinoma ◽

Strong Argument ◽

Poor Prognostic Factor ◽

Fuhrman Grade

Abstract PurposeBrain metastases (BM) usually represent a poor prognostic factor in solid tumors. About 10% of patients with renal cancer (RCC) will present BM. Local therapies such as stereotactic radiotherapy (SRT), whole brain radiotherapy (WBRT), and surgery are used to achieve brain control. We compared survival between patients with synchronous BM (SynBM group) and metachronous BM (MetaBM group). MethodsIt is a retrospective study of patients with clear cell renal cell carcinoma (ccRCC) and BM treated with TKI between 2005 and 2019 at the Centre Léon Bérard in Lyon. We collected prognostic factors: The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk score, the TNM stage, the histological subtypes and the Fuhrman grade. Overall survival (OS) was defined from diagnosis of metastatic ccRCC to death. Brain progression-free survival (B-PFS) was defined from focal brain therapy to brain progression or death.Results99 patients were analyzed, 44 in the SynBM group and 55 in the MetaBM group. OS in the MetaBM group was 49.4 months versus 19.6 months in the SynBM group, p=0.0002. The median time from diagnosis of metastasic disease to apparition of BM in the MetaBM group was 22.9 months (4.3; 125.7). SRT was used for 101 lesions (66.4%), WBRT for 25 patients (16.4%), surgery for 21 lesions (13.8%), surgery followed by radiation for 5 lesions (3.3%). B-PFS for all patients was 7 months (IC95% [5.0-10.5]). ConclusionsSurvival of patients with synchronous BM is inferior to that of patients with metachronous BM. Outcome is poor in both cases after diagnosis of BM. Brain screening should be encouraged at time of diagnosis of metastatis in ccRCC.

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Fumarate hydratase expression in localized, radically-resected clear cell renal cell carcinoma and its association with clinical outcomes.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.620 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 620-620

Author(s):

Giovanni FucÃ ◽

Claudio Vernieri ◽

Simona Massa ◽

Alessia Bertolotti ◽

Giovanna Garzone ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Clinical Outcomes ◽

Relapse Rate ◽

Renal Cell ◽

Clear Cell ◽

Fumarate Hydratase ◽

Cell Renal Cell Carcinoma ◽

Fuhrman Grade ◽

Tubular Cells

620 Background: Prognostic stratification of localized clear cell renal cell carcinoma (lccRCC) mainly relies on clinical characteristics and TNM staging system, while biological biomarkers are currently lacking. We previously showed that reduced expression of the tricarboxylic acid cycle enzyme fumarate hydratase (FH) was associated with better clinical outcomes in patients (pts) with metastatic ccRCC. In the present study we aimed at assessing the association between intratumor FH expression and clinical outcomes in pts with radically-resected lccRCC. Methods: Pts with radically-resected lccRCC and available formalin-fixed, paraffin-embedded (FFPE) primary (renal) tumor tissue were included. FH protein expression was assessed by means of immunohistochemistry (IHC) and defined as normal (comparably to non-neoplastic tubular cells) or low (lower than in non-neoplastic tubular cells). Results: Out of 50 pts included, we found a normal FH expression in 20 cases (40%) and a low FH expression in 30 cases (60%). Median age was 57 years (interquartile range 49-68) and 48 pts (96%) had pN0 disease, while 2 pts (4%) had pN1 disease. Low FH expression was associated with pT ( P= .003) but not with sex, age, Fuhrman grade or pN. After a median follow-up of 76.9 months, low FH expression was associated with a lower relapse rate (13% vs 50%; odds ratio for relapse 0.16; 95% confidence interval [CI] 0.04-0.62; P= .005), longer relapse-free survival (RFS) (5-years RFS rate 90% vs 50%; HR 0.20; 95% CI 0.06-0.63; P= .006) and a trend toward a better overall survival (OS) (5-years OS rate 100% vs 77.3%; HR 0.14; 95% CI 0.02-1.23; P= .07) when compared with normal FH expression. In the multivariable model including other characteristics associated with RFS, low FH expression confirmed an independent association with RFS (adjusted HR 0.25; 95% CI 0.06-0.91; P= .03). Conclusions: In our study, low intratumor FH, as detected by IHC, was associated with lower relapse rate, better RFS and a trend toward a better OS in patients with lccRCC when compared with normal FH levels. The role of FH expression as a prognostic biomarker in this setting warrants further investigation.

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