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Updated: Dec 29, 2025

In Vivo, Percutaneous, Needle Based, Optical Coherence Tomography of Renal Masses
Published on: March 30, 2015
Frequent KRAS mutations in oncocytic papillary renal neoplasm with inverted nuclei
Kuo Tong1,2,3, Wei Zhu1, Hua Fu4
1Department of Pathology, Xiangya Hospital, Central South University, Changsha, China.
Aims:
Papillary renal neoplasm with reverse polarity (PRNRP) is a newly documented rare tumour type. Its molecular pathological features have thus far been very little studied.
Methods And Results:
There were 13 PRNRP cases including 3 The Cancer Genome Atlas (TCGA) cases and our 10 cases in this study. The 3 TCGA cases were found by a combined analysis of GATA3 mRNA expression levels and digital slides from the TCGA papillary renal cell carcinoma project. KRAS codon 12 mutations were identified in the three PRNRPs from TCGA. Of our 10 PRNRP cases, the mutations were also discovered using Sanger sequencing in seven (77.8%) of nine cases with available DNA, where KRAS p.G12V (n = 3), p.G12D (n = 2), p.G12R (n = 1) and p.G12C (n = 1) alterations were found. PRNRP shared similar gene expression profiles with renal distal tubules via an interprofile correlation analysis. Gene set enrichment analysis revealed that genes involved in 'KEGG aldosterone regulated sodium reabsorption' or 'hallmark apical surface' were enriched in PRNRP. Moreover, polarised immunostaining patterns for L1CAM and EMA in the distal tubule were maintained in PRNRP.
Conclusions:
These results imply that the tumour potentially originates from the distal tubule, especially from the cortical collecting duct, and probably retains its cell polarity, except for nuclear inversion. We therefore propose that oncocytic papillary renal neoplasm with inverted nuclei (OPRNIN) is a better name for this tumour type. OPRNIN is a kidney site-specific KRAS mutation neoplasm different from conventional papillary renal cell carcinoma.
Insights
This study reveals that papillary renal neoplasm with reverse polarity (PRNRP) is a rare kidney tumor characterized by KRAS mutations and gene expression profiles similar to distal tubules. Researchers propose renaming it oncocytic papillary renal neoplasm with inverted nuclei (OPRNIN).
Area of Science:
- Oncology
- Molecular Pathology
- Genitourinary Pathology
Background:
- Papillary renal neoplasm with reverse polarity (PRNRP) is a rare tumor type with limited molecular pathological study.
- Understanding its origin and molecular drivers is crucial for accurate diagnosis and classification.
Purpose of the Study:
- To investigate the molecular pathological features of PRNRP.
- To determine the potential cell of origin for PRNRP.
- To propose a more accurate nomenclature for this tumor type.
Main Methods:
- Analysis of 13 PRNRP cases (3 from TCGA, 10 from the study).
- KRAS mutation analysis using Sanger sequencing.
- Gene expression profiling and correlation with renal distal tubules.
- Gene set enrichment analysis and immunohistochemical staining for L1CAM and EMA.
Main Results:
- KRAS codon 12 mutations were identified in 77.8% of available PRNRP cases.
- PRNRP exhibited gene expression profiles similar to renal distal tubules.
- Enrichment of genes involved in 'KEGG aldosterone regulated sodium reabsorption' and 'hallmark apical surface' was observed.
- Polarized immunostaining patterns for L1CAM and EMA were maintained.
Conclusions:
- PRNRP likely originates from the distal tubule, possibly the cortical collecting duct.
- The tumor retains cell polarity despite nuclear inversion.
- The proposed new name, oncocytic papillary renal neoplasm with inverted nuclei (OPRNIN), reflects these findings.
- OPRNIN represents a kidney-specific KRAS-mutated neoplasm distinct from conventional papillary renal cell carcinoma.
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