Abnormal oxidative metabolism in a quiet genomic background underlies clear cell papillary renal cell carcinoma

While genomic sequencing routinely identifies oncogenic alterations for the majority of cancers, many tumors harbor no discernable driver lesion. Here, we describe the exceptional molecular phenotype of a genomically quiet kidney tumor, clear cell papillary renal cell carcinoma (CCPAP). In spite of a largely wild-type nuclear genome, CCPAP tumors exhibit severe depletion of mitochondrial DNA (mtDNA) and RNA and high levels of oxidative stress, reflecting a shift away from respiratory metabolism. Moreover, CCPAP tumors exhibit a distinct metabolic phenotype uniquely characterized by accumulation of the sugar alcohol sorbitol. Immunohistochemical staining of primary CCPAP tumor specimens recapitulates both the depletion of mtDNA-encoded proteins and a lipid-depleted metabolic phenotype, suggesting that the cytoplasmic clarity in CCPAP is primarily related to the presence of glycogen. These results argue for non-genetic profiling as a tool for the study of cancers of unknown driver.

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Clear Cell Papillary Renal Cell Carcinoma

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2018-0121-rs ◽

2019 ◽

Vol 143 (9) ◽

pp. 1154-1158 ◽

Cited By ~ 2

Author(s):

Jianping Zhao ◽

Eduardo Eyzaguirre

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Papillary Renal Cell Carcinoma ◽

Genetic Profiling ◽

Papillary Rcc ◽

High Index Of Suspicion ◽

Cell Changes ◽

Histopathologic Features

Clear cell papillary renal cell carcinoma (ccpRCC) is a recently recognized entity and represents the fourth most common variant of renal cell carcinoma (RCC). It has unique morphologic and immunohistochemical features and demonstrates an indolent clinical behavior. Microscopically, it may mimic other RCCs with clear cell features, such as clear cell RCC, translocation RCC, and papillary RCC with clear cell changes. A high index of suspicion is required to keep ccpRCC in the differential diagnosis of RCCs with features of clear cell and/or papillary architecture. In equivocal cases, immunohistochemistry is generally sufficient to substantiate the diagnosis of ccpRCC. In this review, we discuss the clinical, gross, and histopathologic features, immunohistochemical and genetic profiling, and prognosis of ccpRCC.

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Similarities and Differences between Clear Cell Tubulo-Papillary and Conventional Clear Cell Renal Cell Carcinoma: A Comparative Phenotypical and Mutational Analysis

Diagnostics ◽

10.3390/diagnostics10020123 ◽

2020 ◽

Vol 10 (2) ◽

pp. 123

Author(s):

Francesca Giunchi ◽

Tania Franceschini ◽

Elisa Gruppioni ◽

Annalisa Altimari ◽

Elisa Capizzi ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Differential Diagnosis ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Mutational Analysis ◽

Papillary Renal Cell Carcinoma ◽

Tumor Type ◽

Wild Type ◽

Cell Renal Cell Carcinoma

Background: Clear cell tubulo-papillary renal cell carcinoma (cctpRCC) is characterized by clear cell morphology, but differs from conventional clear cell carcinoma (ccRCC) for its indolent clinical behavior and genetic background. The differential diagnosis between the two is based on histology and immunohistochemistry (IHC). Methods: We performed a comparative case-control histological, IHC, and genetic analysis by next generation sequencing (NGS), to point out the differences in 10 cases of cctpRCC, and six controls of ccRCC with low stage and grade. Results: All 16 cases showed the IHC profile with cytokeratin 7, racemase, and carbonic anhydrase IX expected for the histological features of each tumor type. By contrast, the NGS mutation analysis that covered 207 amplicons of 50 oncogenes or tumor suppressor genes provided conflicting results. Among the 10 cctpRCC cases, eight (80%) were wild type for all of the genes in the panel, while two (20%) harbored VHL mutations typical of ccRCC. Three of the six (50%) ccRCC control cases showed expected VHL mutations; two (33%) harbored pathogenic mutations in the p53 or the CKIT genes; and one (16%) was wild type. Conclusion: We can assume that histology and ICH are not sufficient for a definitive diagnosis of cctpRCC or ccRCC. Although with a panel covering 50 genes, we found that 80% of cctpRCC were genetically silent; thus, suggesting an indolent biology of these tumors. The differential diagnosis between ccptRCC and ccRCC for the choice of the best therapeutic strategy likely requires the comprehensive evaluation of histology, IHC, and at least VHL mutations.

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Clear cell (Tubulo) papillary renal cell carcinoma: Case report

10.26226/morressier.578f37fbd462b8028d8904a2 ◽

2016 ◽

Author(s):

Ulku Kazanci

Keyword(s):

Renal Cell Carcinoma ◽

Case Report ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Papillary Renal Cell Carcinoma ◽

Renal Cell Carcinoma Case

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Re: Stanley Weng, Renzo G. DiNatale, Andrew Silagy, et al. The Clinicopathologic and Molecular Landscape of Clear Cell Papillary Renal Cell Carcinoma: Implications in Diagnosis and Management. Eur Urol 2021;79:468–77

European Urology ◽

10.1016/j.eururo.2021.05.011 ◽

2021 ◽

Author(s):

Sounak Gupta ◽

Beth A. Pitel ◽

Shannon M. Knight ◽

Kevin C. Halling ◽

Rafael E. Jimenez ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Papillary Renal Cell Carcinoma ◽

Diagnosis And Management ◽

Molecular Landscape

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Mutation associated with Fanconi anemia pathway may increase patients’ second primary malignancy risk: Results from somatic and germline testing of clear cell papillary renal cell carcinoma

European Urology ◽

10.1016/s0302-2838(21)01088-5 ◽

2021 ◽

Vol 79 ◽

pp. S980

Author(s):

X. Tian ◽

A. Aihetaimujiang ◽

Y.Y. Qu ◽

H.L. Zhang ◽

D.W. Ye

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Fanconi Anemia ◽

Renal Cell ◽

Clear Cell ◽

Papillary Renal Cell Carcinoma ◽

Second Primary ◽

Second Primary Malignancy ◽

Primary Malignancy ◽

Germline Testing

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Down-regulation of BCL2L13 renders poor prognosis in clear cell and papillary renal cell carcinoma

Cancer Cell International ◽

10.1186/s12935-021-02039-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Fei Meng ◽

Luojin Zhang ◽

Mingjun Zhang ◽

Kaiqin Ye ◽

Wei Guo ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Kidney Cancer ◽

Renal Cell ◽

Poor Prognosis ◽

Clear Cell ◽

Papillary Renal Cell Carcinoma ◽

Functional Enrichment ◽

Cancer Tissue ◽

Down Regulation

Abstract Background BCL2L13 belongs to the BCL2 super family, with its protein product exhibits capacity of apoptosis-mediating in diversified cell lines. Previous studies have shown that BCL2L13 has functional consequence in several tumor types, including ALL and GBM, however, its function in kidney cancer remains as yet unclearly. Methods Multiple web-based portals were employed to analyze the effect of BCL2L13 in kidney cancer using the data from TCGA database. Functional enrichment analysis and hubs of BCL2L13 co-expressed genes in clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) were carried out on Cytoscape. Evaluation of BCL2L13 protein level was accomplished through immunohistochemistry on paraffin embedded renal cancer tissue sections. Western blotting and flow cytometry were implemented to further analyze the pro-apoptotic function of BCL2L13 in ccRCC cell line 786-0. Results BCL2L13 expression is significantly decreased in ccRCC and pRCC patients, however, mutations and copy number alterations are rarely observed. The poor prognosis of ccRCC that derived from down-regulated BCL2L13 is independent of patients’ gender or tumor grade. Furthermore, BCL2L13 only weakly correlates with the genes that mutated in kidney cancer or the genes that associated with inherited kidney cancer predisposing syndrome, while actively correlates with SLC25A4. As a downstream effector of BCL2L13 in its pro-apoptotic pathway, SLC25A4 is found as one of the hub genes that involved in the physiological function of BCL2L13 in kidney cancer tissues. Conclusions Down-regulation of BCL2L13 renders poor prognosis in ccRCC and pRCC. This disadvantageous factor is independent of any well-known kidney cancer related genes, so BCL2L13 can be used as an effective indicator for prognostic evaluation of renal cell carcinoma.

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