Molecular profile of early-stage and advanced-stage of renal cell cancer in China.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16071-e16071
Author(s):  
Jimin Chen ◽  
Yanrui Zhang ◽  
Tongtong Yang ◽  
Huina Wang ◽  
Jing Guo ◽  
...  
Keyword(s):  
Renal Cell Cancer ◽  
Renal Cell ◽  
Early Stage ◽  
Clinical Status ◽  
Cell Cancer ◽  
Genetic Alterations ◽  
Molecular Profile ◽  
Molecular Characteristics ◽  
Advanced Stage ◽  
Genomic Alterations

e16071 Background: The mutation spectrum has been extensively studied in Renal Cell Cancer (RCC), a heterogeneous disease. While major investigations have focused on metastatic RCC (mRCC). This study intended to explore the molecular characteristics between early-stage (stage I/Ⅱ) and advanced-stage (Ⅲ/Ⅳ) of RCC patients (pts). Methods: 36 tumor specimens were obtained from individual pts diagnosed RCC, including 22 tissues paired with blood samples. Somatic mutations were identified via targeted next generation sequencing with Acornmed panel including 808 genes associated with tumor development. Sequencing data were analyzed to call tumor specific single nucleotide variants (SNV), small insertions and deletions (InDels), copy number alterations (CNA) and chromosomal rearrangements. Clinical data of a cohort from TCGA who had RCC was collected and analyzed. Results: Among the 36 pts enrolled, 61% were early-stage group and 39% were advanced-stage group. The most frequently mutated genes in RCC were VHL (50%), PBRM1 (14%), BAP1 (11%), TP53 (11%) and PIK3CA (6%). Truncating mutations were the most frequent alterations accounting for 66% (33/50) of genetic alterations. Mutations in VHL, BAP1, PBRM1 and TP53 were shared by both early and advanced RCC. While mutations in PIK3CA, CDKN2C, EGFR, FAMCA, GRIN2A, KDM6A, SOX17, TSC1 and APC were only detected in early stage group. KNSTRN, KRAS, MYD88, NF2, ATM, PTEN and STAT5B mutations were only detected in advanced group. Among 22 plasma samples, genomic alterations were detected in 40.9% (9/22) of pts postoperatively, such as TP53, PIK3CA, PTEN, and APC. Functional annotation clustering revealed that 4/9 in these genes were tumor suppressors, which negatively regulated apoptosis. Pts with genomic alterations in TP53 (p = 0.0034), PIK3CA (p = 0.0015) or PTEN (p = 0.00017) had worse OS significantly (TCGA). Conclusions: VHL, PBRM1, BAP1 were the most important driver genes mainly detected in all stages of RCC. The heterogeneity between early and advanced-stage may be related with clinical status. Gene alterations in plasma ctDNA postoperatively should have the potential to stratify patients with different prognostic outcome.

644: Cathepsin D is a Marker for Early Stage Renal Cell Cancer and Predicts the Presence of Distant Metastases

2005 ◽  
Vol 173 (4S) ◽  
pp. 175-175
Author(s):  
Axel S. Merseburger ◽  
Joerg Hennenlotter ◽  
Perikles Simon ◽  
Marcus Horstmann ◽  
Arnulf Stenzl ◽  
...  
Keyword(s):  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cathepsin D ◽  
Early Stage ◽  
Cell Cancer ◽  
Distant Metastases

Impact of tumor size on the long-term survival of patients with early stage renal cell cancer

2005 ◽  
Vol 23 (1) ◽  
pp. 50-54 ◽  
Author(s):  
M. Kuczyk ◽  
G. Wegener ◽  
A. S. Merseburger ◽  
A. Anastasiadis ◽  
S. Machtens ◽  
...  
Keyword(s):  
Renal Cell Cancer ◽  
Tumor Size ◽  
Renal Cell ◽  
Early Stage ◽  
Cell Cancer ◽  
Term Survival ◽  
Long Term Survival

36 Cathepsin D is a marker for early stage renal cell cancer and predicts the presence of distant metastases

2005 ◽  
Vol 4 (3) ◽  
pp. 11
Author(s):  
A.S. Merseburger ◽  
J. Hennenlotter ◽  
P. Simon ◽  
M. Horstmann ◽  
S. Kruck ◽  
...  
Keyword(s):  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cathepsin D ◽  
Early Stage ◽  
Cell Cancer ◽  
Distant Metastases

Clear Cell Renal Cell Cancer Tumor-Propagating Cells: Molecular Characteristics

2014 ◽  
Vol 8 (3) ◽  
pp. 229-239 ◽  
Author(s):  
Damian Matak ◽  
Lukasz Szymanski ◽  
Anna Czarnecka ◽  
Ewa Bartnik ◽  
Cezary Szczylik
Keyword(s):  
Renal Cell Cancer ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Cancer ◽  
Molecular Characteristics ◽  
Cancer Tumor

A phase II study of bevacizumab and erlotinib in subjects with advanced hereditary leiomyomatosis and renal cell cancer (HLRCC) or sporadic papillary renal cell cancer (RCC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4680-TPS4680 ◽  
Author(s):  
Eric A. Singer ◽  
Julia C. Friend ◽  
Geri Hawks ◽  
Cathy Vocke ◽  
Adam R. Metwalli ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phase Ii ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Transforming Growth Factor ◽  
Phase Ii Study ◽  
Cell Cancer ◽  
Fumarate Hydratase ◽  
Genetic Alterations ◽  
Papillary Rcc

TPS4680 Background: There are currently no treatment options of proven efficacy for patients with advanced papillary RCC. The evaluation of families with inherited forms of RCC has allowed for the identification of genetic alterations associated with papillary RCC. HLRCC is one such familial condition with a propensity for the development of a clinically aggressive variant of papillary RCC characterized by unique histopathologic features. Germline mutations in the gene for the Krebs cycle enzyme fumarate hydratase (FH) are the genetic hallmark of HLRCC. Mutational inactivation of FH leads to von Hippel-Lindau-independent upregulation of hypoxia inducible factors (HIF) and their downstream transcriptional targets such as vascular endothelial growth factor (VEGF) and transforming growth factor-alpha (TGF-α) / epidermal growth factor receptor (EGFR). Upregulation of the HIF pathway may also be important in sporadic papillary RCC, although the prevalence of FH inactivation in these patients is unknown. We propose to evaluate the activity of dual VEGF/EGFR blockade with bevacizumab/erlotinib in patients with HLRCC-associated RCC and sporadic papillary RCC. Methods: This is a single arm phase II study based on an open label Simon two-stage minmax design with a maximum accrual of 20 patients in each of two cohorts: Cohort 1- patients with HLRCC; Cohort 2- patients with sporadic papillary RCC. The primary endpoint is RECIST overall response rate, assessed independently in each cohort. Patients will receive bevacizumab (10mg/Kg IV every 2 weeks) and erlotinib (150mg PO daily). Dose reductions and drug interruptions for toxicity are allowed. Patients will be evaluated for response every 8 weeks. Major eligibility criteria include: advanced RCC associated with HLRCC or sporadic papillary RCC; age >18 years; ECOG 0-2; measurable disease by RECIST; no brain metastases; no more than 2 prior regimens containing a VEGF inhibitor; and no prior therapy with bevacizumab. The prespecified activity goal for the first stage of accrual has been met for both cohorts. NCT01130519.

New aspects on the identification of genetic alterations and prognostically important biological parameters in renal cell cancer

Der Urologe ◽  
1999 ◽  
Vol 38 (5) ◽  
pp. 442-451
Author(s):  
S. Machtens ◽  
M. Kuczyk ◽  
A. J. Becker ◽  
C. Bokemeyer ◽  
J. Serth ◽  
...  
Keyword(s):  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Genetic Alterations ◽  
Biological Parameters

Survival outcomes of sarcomatoid renal cell cancer (sRCC) compared to clear cell renal cell cancer (ccRCC): An analysis of SEER data.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17101-e17101
Author(s):  
Ruby Gupta ◽  
Filip Ionescu ◽  
Vishal Jindal ◽  
John Khoury ◽  
Nwabundo Ifeyinwa Anusim ◽  
...  
Keyword(s):  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Histologic Grade ◽  
Advanced Stage ◽  
Seer Database ◽  
Small Component ◽  
Female Ratio ◽  
Seer Data ◽  
Disease Specific

e17101 Background: Renal cell carcinoma (RCC) with sarcomatoid differentiation is a highly aggressive form of RCC. The presence of even a small component of sRCC was shown to independently predict poor survival compared to RCC without sarcomatoid features. We studied the epidemiology and survival outcome of sRCC compared to ccRCC by reviewing the SEER data. Methods: Patients (pts) with histologically confirmed sRCC and ccRCC between 2012-2015 were reviewed in SEER database. Variables included age, gender, ethnicity, histologic grade, stage at diagnosis, and nephrectomy. Primary outcome was 5 year Disease Specific Survival (DSS). Data was analyzed using Kaplan Meier curves and Cox proportional hazards model. Results: A total of 31, 293 pts with RCC were identified in SEER database between 2012 to 2015. 611 pts had sRCC while 30, 682 had ccRCC. The two groups had almost similar demographic features, including mean age (63 ±12 for sRCC vs 61±12 years for ccRCC), male: female ratio (vs 2.3:1 vs 1.7:1) and Caucasian ethnicity (82% vs 85%). More than half of sRCC patients (62%) were metastatic at diagnosis compared to only 11% of ccRCC, which presented most commonly as stage I disease (63%). The histologic grade was higher in sRCC patients (43% grade 4 vs 45% grade 2 in ccRCC subjects). Nephrectomy rates were almost similar for stages I-III in the two groups (94% in sRCC vs 93% in ccRCC) while lower in stage IV sRCC (44% vs 54%). Across all stages and at every time point, sRCC was associated with increased mortality in the univariate analysis. In the multivariate regression analysis (table), advanced stage was the strongest independent predictor of mortality (HR 11.9), followed by high histologic grade (HR 3.6) and sarcomatoid histology (HR 2.9). Nephrectomy was protective (HR 0.3). Age was associated with worse outcomes (HR 1.016 per unit change). Conclusions: sRCC are more aggressive and tend to present as metastatic disease. sRCC has worse outcomes across all stages compared to ccRCC even after adjusting for potential confounders. Advanced stage and histologic grade remain the two strongest predictors of disease-specific mortality, sarcomatoid histology demonstrated a significant impact on outcome. [Table: see text]

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