Differential immunohistochemical and molecular profiling of conventional and aggressive components of chromophobe renal cell carcinoma: pitfalls for diagnosis

Chen, Constance V.; Croom, Nicole A.; Simko, Jeffry P.; Stohr, Bradley A.; Chan, Emily

doi:10.1016/j.humpath.2021.11.003

Cited by 6 publications

(5 citation statements)

References 27 publications

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“…Although CDH16 expression differences between renal cancer subtypes are statistically significant, our data do not suggest a relevant practical utility of CDH16 immunohistochemistry for subtype distinction at the selected experimental conditions. This is also because of the striking utility of CD117 for this distinction 42 , 43 . We previously found a significant link between low CDH16 expression and unfavorable tumor phenotype and poor prognosis in clear cell RCC which may argue for a functional role of CDH16 expression loss in the progression of these tumors 44 .…”

Section: Discussionmentioning

confidence: 99%

Cadherin-16 (CDH16) immunohistochemistry: a useful diagnostic tool for renal cell carcinoma and papillary carcinomas of the thyroid

Lennartz

Csomós

Chirico

et al. 2023

Sci Rep

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Cadherin-16 (CDH16) plays a role in the embryonal development in kidney and thyroid. Downregulation of CDH16 RNA was found in papillary carcinomas of the thyroid. To determine the expression of CDH16 in tumors and to assess the diagnostic utility a tissue microarray containing 15,584 samples from 152 different tumor types as well as 608 samples of 76 different normal tissue types was analyzed. A membranous CDH16 immunostaining was predominantly seen in thyroid, kidney, cauda epididymis, and mesonephric remnants. In the thyroid, CDH16 staining was seen in 100% of normal samples, 86% of follicular adenomas, 60% of follicular carcinomas, but only 7% of papillary carcinomas (p < 0.0001). CDH16 positivity was frequent in nephrogenic adenomas (100%), oncocytomas (98%), chromophobe (97%), clear cell (85%), and papillary (76%) renal cell carcinomas (RCCs), various subtypes of carcinoma of the ovary (16–56%), various subtyped of carcinomas of the uterus (18–40%), as well as in various subtypes of neuroendocrine neoplasms (4–26%). Nineteen further tumor entities showed a weak to moderate CDH16 staining in up to 8% of cases. Our data suggest CDH16 as a potential diagnostic marker—as a part of a panel—for the identification of papillary carcinomas of the thyroid, nephrogenic adenomas, and the distinction of renal cell tumors from other neoplasms.

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Section: Discussionmentioning

confidence: 99%

Cadherin-16 (CDH16) immunohistochemistry: a useful diagnostic tool for renal cell carcinoma and papillary carcinomas of the thyroid

Lennartz

Csomós

Chirico

et al. 2023

Sci Rep

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show abstract

“…The differential gene expression patterns enriched in cell growth and expansion suggest that chRCC may have a higher proliferative capacity compared to the other two tumor samples (Figure S10B), which is consistent with its aggressive clinical behavior. 24,25 MA is a rare benign renal neoplasm that accounts for ∼0.2% of renal epithelial neoplasms. 17 For the first time, we have characterized the transcriptome of MA at the single-cell level.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Well-Paired-Seq2: High-Throughput and High-Sensitivity Strategy for Characterizing Low RNA-Content Cell/Nucleus Transcriptomes

Yin,

Zhao,

et al. 2024

Anal. Chem.

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Single-cell RNA sequencing (scRNA-seq) is a transformative technology that unravels the intricate cellular state heterogeneity. However, the Poisson-dependent cell capture and low sensitivity in scRNA-seq methods pose challenges for throughput and samples with a low RNA-content. Herein, to address these challenges, we present Well-Paired-Seq2 (WPS2), harnessing sizeexclusion and quasi-static hydrodynamics for efficient cell capture. WPS2 exploits molecular crowding effect, tailing activity enhancement in reverse transcription, and homogeneous enzymatic reaction in the initial bead-based amplification to achieve 3116 genes and 8447 transcripts with an average of ∼20000 reads per cell. WPS2 detected 1420 more genes and 4864 more transcripts than our previous Well-Paired-Seq. It sensitively characterizes transcriptomes of low RNA-content single cells and nuclei, overcoming the Poisson limit for cell and barcoded bead capture. WPS2 also profiles transcriptomes from frozen clinical samples, revealing heterogeneous tumor copy number variations and intercellular crosstalk in clear cell renal cell carcinomas. Additionally, we provide the first single-cell-level characterization of rare metanephric adenoma (MA) and uncover potential specific markers. With the advantages of high sensitivity and high throughput, WPS2 holds promise for diverse basic and clinical research.

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Section: Resultsmentioning

confidence: 99%

“…The differential gene expression patterns enriched in cell growth and expansion suggest that chRCC may have a higher proliferative capacity compared to the other two tumor samples (Figure 6F), which is consistent with its aggressive clinical behavior. 30,31 MA is a rare benign renal neoplasm that accounts for ~0.2% of adult renal epithelial neoplasms. 21 For the first time, we characterized the transcriptome of MA at the single-cell level.…”

Section: Wps2 For Clinical Sample Analysismentioning

confidence: 99%

Well-Paired-Seq2: High-Throughput and High-Sensitivity Strategy for Characterizing Low RNA-Content Cell/Nucleus Transcriptomes

Yin,

Zhao,

et al. 2023

Preprint

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High-throughput single-cell RNA sequencing (scRNA-seq) is recognized as a powerful technology for disentangling the heterogeneity of cellular states. However, the Poisson-dependent cell capture and low sensitivity in scRNA-seq methods pose challenges for throughput and for samples with low RNA-content. Herein, to address these challenges, we developed Well-Paired-Seq2 (WPS2) based on size-exclusion and locally quasi-static hydrodynamic principles to realize high efficiency of cell utilization, single cell/bead pairing, and cell-free RNA removal. WPS2 exploits molecular crowding effect, tailing activity enhancement in reverse transcription, and homogeneous enzymatic reaction in the initial bead-based amplification to achieve 3116 genes and 8447 transcripts. With an average of ∼20,000 reads per cell, WPS2 detected 1420 more genes and 4864 more transcripts than our previous Well-Paired-Seq. Using WPS2, we overcame the Poisson limit for the capture of both cells and beads and accurately characterized transcriptomes of low RNA-content single cells and nuclei with high sensitivity. WPS2 was further applied to comprehensively profile transcriptomes from frozen clinical samples. We found that clear cell renal cell carcinoma (ccRCC) has a complex microenvironment, and that chromophobe renal cell carcinoma (chRCC) exhibits abundant copy number variations (CNVs). In addition, metanephric adenoma (MA) was characterized at single-cell level for the first time and some potentially specific markers were revealed. With the advantages of high sensitivity, high throughput, and high fidelity, we anticipate that WPS2 will be broadly applicable in basic and clinical research.

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Differential immunohistochemical and molecular profiling of conventional and aggressive components of chromophobe renal cell carcinoma: pitfalls for diagnosis

Cited by 6 publications

References 27 publications

Cadherin-16 (CDH16) immunohistochemistry: a useful diagnostic tool for renal cell carcinoma and papillary carcinomas of the thyroid

Cadherin-16 (CDH16) immunohistochemistry: a useful diagnostic tool for renal cell carcinoma and papillary carcinomas of the thyroid

Well-Paired-Seq2: High-Throughput and High-Sensitivity Strategy for Characterizing Low RNA-Content Cell/Nucleus Transcriptomes

Well-Paired-Seq2: High-Throughput and High-Sensitivity Strategy for Characterizing Low RNA-Content Cell/Nucleus Transcriptomes

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