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

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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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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Correlation between MVD and Two Prognostic Factors: Fuhrman Grade and Tumoral Size, in Clear Cell Renal Cell Carcinoma

Journal of Cancer Science & Therapy ◽

10.4172/1948-5956.1000160 ◽

2012 ◽

Vol 04 (10) ◽

Cited By ~ 1

Author(s):

Colaci Pablo

Keyword(s):

Renal Cell Carcinoma ◽

Prognostic Factors ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Fuhrman Grade

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

Oncology Letters ◽

10.3892/ol.2020.11498 ◽

2020 ◽

Author(s):

Naimeng Yan ◽

Xue Feng ◽

Sixiong Jiang ◽

Weibin Sun ◽

Ming‑Zhong Sun ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Tnm Stage ◽

Cell Renal Cell Carcinoma ◽

Fuhrman Grade

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Toward a molecular genetic classification of clear cell renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.341 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 341-341

Author(s):

James Brugarolas ◽

Payal Kapur ◽

Samuel Pena-Llopis ◽

Alana Christie ◽

Xian-Jin Xie

Keyword(s):

Gene Expression ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

The Cancer Genome Atlas ◽

Genetic Classification ◽

Cell Renal Cell Carcinoma ◽

Fuhrman Grade ◽

Pathologic Features

341 Background: Clear cell renal cell carcinoma (ccRCC) displays a variety of clinical behaviors. However, the molecular underpinnings are unknown. We discovered that BAP1 is mutated in approximately 15% of ccRCC and that BAP1 and PBRM1mutations are largely mutually exclusive. Herein, we investigate the clinicopathological significance of these molecular subtypes. Methods: Tumors from 145 patients with primary ccRCC were sequenced for PBRM1 and BAP1. Tumors were classified into BAP1-mutated and those exclusively mutated for PBRM1. Tumors were evaluated for pathologic features, gene expression and associated outcomes. A second independent cohort (n=327) from The Cancer Genome Atlas (TCGA) was used for validation. Results: When compared to PBRM1-mutant tumors, BAP1-mutant tumors were associated with aggressive pathological features including high Fuhrman grade and tumor necrosis. BAP1-mutant and PBRM1-mutant tumors exhibited distinct gene expression signatures. The median overall survival (OS) was shorter for patients with BAP1-mutant tumors (4.6 years; 95% CI, 2.1-7.2), than for patients with PBRM1-mutant tumors (10.6 years; 95% CI, 9.8-11.5), corresponding to a hazard ratio (HR) of 2.7 (95% CI, 0.99-7.6, p = 0.044). A similar HR was observed in the independent dataset from the TCGA (2.8; 95% CI, 1.4-5.9; p = 0.004). The BAP1-mutant group could be further subdivided into tumors with mutations exclusively in BAP1 and those with mutations in both BAP1 and PBRM1. Double mutant tumors constituted a minority (n = 4; in TCGA), and were associated with the shortest OS (HR, 10; 95% CI, 3.2-33.6). Conclusions: Our findings reveal novel biological subgroups of ccRCC with distinct clinical outcomes, a high-risk BAP1-mutant group and a favorable PBRM1-mutant group. These data establish the basis for a molecular subclassification of ccRCC that could influence treatment decisions in the future.

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