Renal Sinus Fat Invasion in pT3a Clear Cell Renal Cell Carcinoma Affects Outcomes of Patients Without Nodal Involvement or Distant Metastases

Clear cell renal cell carcinoma (ccRCC) is an heterogeneous tumour at architectural, cellular and molecular level, a reason why the 2014 International Society of Urological Pathology consensus recommended wide sampling of RCC masses to include at least 1 block/cm of tumour together with perpendicular sections of the tumour/perinephric fat interface and the tumour/renal sinus interface. Intratumoural molecular heterogeneity may be a limitation at the moment of defining precision medicine strategies based on gene mutation status. This study analyses the presence of any mutation of KRAS, NRAS, BRAF, PIK3CA, ALK, ERBB2, DDR2, MAP2K1, RET and EGFR genes in 20 tissue blocks from a case of ccRCC and its metastasis. We observed the presence of the mutation at pH1047R of PIK3CA gene in five samples of the tumour, while the remaining 15 samples did not show any mutation at PIK3CA or any other investigated gene. There is a great need to develop novel RCC sampling strategies to overcome tumour heterogeneity prior to define precision oncology strategies.

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Prognostic evaluation of perinephric fat, renal sinus fat, and renal vein invasion for patients with pathological stage T3a clear-cell renal cell carcinoma

BJU International ◽

10.1111/bju.14523 ◽

2018 ◽

Vol 123 (2) ◽

pp. 270-276 ◽

Cited By ~ 10

Author(s):

Paras H. Shah ◽

Timothy D. Lyon ◽

Christine M. Lohse ◽

John C. Cheville ◽

Bradley C. Leibovich ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Renal Cell ◽

Renal Vein ◽

Clear Cell ◽

Pathological Stage ◽

Cell Renal Cell Carcinoma ◽

Renal Sinus ◽

Prognostic Evaluation ◽

Renal Sinus Fat ◽

Perinephric Fat

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Contact with renal sinus is associated with poor prognosis in surgically treated pT1 clear cell renal cell carcinoma

International Journal of Urology ◽

10.1111/iju.14266 ◽

2020 ◽

Vol 27 (8) ◽

pp. 657-662 ◽

Cited By ~ 1

Author(s):

Keita Izumi ◽

Kazutaka Saito ◽

Takayuki Nakayama ◽

Shohei Fukuda ◽

Hiroshi Fukushima ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Poor Prognosis ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Renal Sinus

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459 ANALYSIS OF SITE SPECIFIC MIRNA EXPRESSION IN DISTANT METASTASES OF CLEAR CELL RENAL CELL CARCINOMA

The Journal of Urology ◽

10.1016/j.juro.2013.02.1850 ◽

2013 ◽

Vol 189 (4S) ◽

Author(s):

Joana Heinzelmann ◽

Sophie Baumgart ◽

Ulrike Wickmann ◽

Andre Unrein ◽

Attila Szendroi ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Mirna Expression ◽

Renal Cell ◽

Clear Cell ◽

Distant Metastases ◽

Cell Renal Cell Carcinoma ◽

Site Specific

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Collision Tumor of the Kidney with Clear Cell Renal Cell Carcinoma and Papillary Renal Cell Carcinoma Components: Report of a Rare Case

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa161.139 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S64-S64

Author(s):

S R Avalos Hernandez ◽

S Liu ◽

F Sameeta ◽

W Mneimneh

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Collision Tumor ◽

Renal Tumors ◽

Vimentin Expression ◽

Cell Renal Cell Carcinoma ◽

Renal Sinus ◽

Collision Tumors

Abstract Introduction/Objective Collision tumors refer to the phenomenon where distinct, well-defined tumor subtypes are present within a single lesion. While this phenomenon has been described in different organs, it has been rarely encountered in renal tumors outside the context of rare tumor susceptibility syndromes. Collision tumors of the kidney may encompass any known benign or malignant renal tumor types. However, a collision tumor of two different renal cell carcinoma (RCC) subtypes is remarkably rare. Methods A 43-year-old male was referred to our institution for the management of a right lower pole renal mass. The right radical nephrectomy specimen revealed a 6.5 x 5.0 x 4.0 cm well circumscribed, yellow-orange and hemorrhagic cortical mass abutting the renal capsule and extending into the renal sinus fat. A grossly distinct 1.5 x 1.4 x 1.2 cm pale, nodular area was demonstrated at the periphery of the tumor. Results Microscopically, the tumor displayed two distinct, neoplastic components within the same mass, without transitional morphology. The majority of the tumor consisted of a nuclear-grade-2 conventional clear cell RCC, while the peripheral nodule represented a type-2 papillary RCC component. Immunostains further supported these findings: The papillary component was strongly and diffusely positive for CK7 and P504S/AMACR with variable EMA and vimentin expression, and negative for CAIX, while the clear cell component was positive for CAIX, EMA and vimentin with only focal and weak staining for CK7 and faint nonspecific P5O4S/AMACR staining. TFE3 Mart1 and HMB45 immunostains were negative in the tumor. Conclusion Collision tumor of the kidney with two distinct RCC subtypes is an exceedingly rare finding. Careful gross examination may be the first clue to identify such lesions, and sampling of all grossly distinct tumor areas is crucial. The identification of collision tumors may have important therapeutic implications, given the difference in pathophysiology and outcome between RCC subtypes.

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MicroRNAs with Prognostic Potential for Metastasis in Clear Cell Renal Cell Carcinoma: A Comparison of Primary Tumors and Distant Metastases

Annals of Surgical Oncology ◽

10.1245/s10434-013-3361-3 ◽

2013 ◽

Vol 21 (3) ◽

pp. 1046-1054 ◽

Cited By ~ 41

Author(s):

Joana Heinzelmann ◽

André Unrein ◽

Ulrike Wickmann ◽

Sophie Baumgart ◽

Marcus Stapf ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Distant Metastases ◽

Cell Renal Cell Carcinoma ◽

Primary Tumors

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Patterns of distant metastases in patients with clear cell renal cell carcinoma––A population‐based analysis

Cancer Medicine ◽

10.1002/cam4.3596 ◽

2020 ◽

Author(s):

Jianxin Xue ◽

Wensun Chen ◽

Wenbo Xu ◽

Zicheng Xu ◽

Xiao Li ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Distant Metastases ◽

Population Based ◽

Cell Renal Cell Carcinoma

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AGAP2-AS1 as a potential marker for development of distant metastases in surgically treated low-risk clear cell renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.732 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 732-732

Author(s):

Sigrid Nakken ◽

Øystein Eikrem ◽

Hans-Peter Marti ◽

Christian Beisland ◽

Leif Bostad ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Distant Metastases ◽

Low Risk ◽

Rna Seq ◽

Cell Renal Cell Carcinoma ◽

Fixed Tissue ◽

Fuhrman Grade

732 Background: Historically, 30 % of patients with localized kidney cancer develop distant metastases during follow-up. There is an urgent need to improve the individual risk assessment for clear cell renal cell carcinoma (ccRCC) patients. We therefore aim to characterize the gene expression profile of low-risk patients both with and without progressive disease to define predictive outcome candidate markers. Methods: Formalin-fixed tissue blocks from ccRCC patients (n=24, eight progressors and 16 non-progressors) with a low Leibovich score were collected. Patients had a mean age of 65 years (5 females and 19 males). The non-progressors were matched 2:1 to the progressors for gender, age, pT tumor stage, size, Fuhrman grade, and eGFR. Total RNA was extracted(miRNeasy FFPE Kit, Qiagen) and sequenced (TruSeq RNA Access Library Kit, Illumina). RNA-seq results were analyzed by ingenuity pathway analysis, K Nearest Neighbors algorithm, and survival analysis. Results: 1167 differentially expressed genes (abs.FC≥2, p≤0.05) were detected. Progressors overexpressed genes related to cancer, B-cell infiltration and other immune-system related pathways. Principal component analyses and hierarchical clustering depicted a systematic transcriptomic difference between progressors and non-progressors. Combinations of up to 10 genes were evaluated as classifiers. The AGAP2-AS1 mRNA classified 23 out of 24 samples correctly, without the need for a larger gene panel. The trend of expression was confirmed with RT-PCR.The correlation between sample status as either progressor or non-progressor and AGAP2-AS1 level was R2 =0.69, p <0.01. Patients were split into groups based on AGAP2-AS1 expression (cut-off log2cpm>1), where higher expression correlated with shorter survival; Wilcoxon (p<0.0001),Log-rank test (p<0.0001), Hazard ratio; 9.24E-11. Immunohistochemistry of AGAP2, USP10 and KI-67 confirmed results from the mRNA level. Conclusions: RNA-seq results show a transcriptomic difference between low-risk ccRCC progressors and low-risk non-progressors. AGAP2-AS1 may serve as a potential classifier for the identification of low-risk progressors.

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