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.

Histopathology
|January 31, 2020
PubMed
Abstract

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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