Recurrent KRAS mutations in papillary renal neoplasm with reverse polarity

Al‐Obaidy, Khaleel I; Eble, John N.; Nassiri, Mehdi; Cheng, Liang; Eldomery, Mohammad K.; Williamson, Sean R.; Sakr, Wael; Gupta, Nilesh; Hassan, Oudai; Idrees, Muhammad T.; Grignon, David J.

doi:10.1038/s41379-019-0362-1

Cited by 52 publications

(49 citation statements)

References 25 publications

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“…Most recently, recurrent KRAS mutations at hot‐spot codon 12 in eight (80%) of 10 PRNRP cases were previously found by Al‐Obaidy et al 35 . using next‐generation sequencing, which occurred during our ongoing experiment.…”

Section: Discussionsupporting

confidence: 52%

Frequent KRAS mutations in oncocytic papillary renal neoplasm with inverted nuclei

Tong

Zhu

et al. 2020

Histopathology

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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 (OPR-NIN) is a better name for this tumour type. OPRNIN is a kidney site-specific KRAS mutation neoplasm different from conventional papillary renal cell carcinoma.

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Section: Discussionsupporting

confidence: 52%

Frequent KRAS mutations in oncocytic papillary renal neoplasm with inverted nuclei

Tong

Zhu

et al. 2020

Histopathology

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“…Varied papillary lesions, including intraductal papillary mucinous neoplasms of the pancreas and urothelial papillomas of the bladder, also have frequent KRAS mutations [ 13 , 14 ]. KRAS mutations are rare events in kidney tumors, however, it has recently been found to be a characteristic feature of PRNRP as reported by multiple studies, including the current reported cases [ 15 – 17 ].…”

Section: Discussionmentioning

confidence: 53%

Unilateral synchronous papillary renal neoplasm with reverse polarity and clear cell renal cell carcinoma: a case report with KRAS and PIK3CA mutations

et al. 2020

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Background The presence of histologically different neoplasms in the same organ is rare in pathologic practice. We report the first case of synchronous clear cell renal cell carcinoma (clear cell RCC) and papillary renal neoplasm with reverse polarity (PRNRP) with comprehensive immunohistochemical and molecular characterization using next-generation sequencing (NGS). Case presentation A 61-year-old man was incidentally found to have a left renal mass on imaging studies performed for workup of left back pain and urine color change for 1 week. A laparoscopic left radical nephrectomy was performed. Gross examination showed lobulated masses measuring 5.6 × 4.0 × 3.3 cm in the upper to mid pole and 1.1 × 1.0 × 1.0 cm in the lower pole. Microscopic findings revealed these to be two different separate masses of clear cell renal cell carcinoma and papillary renal neoplasm with reverse polarity. NGS analyses revealed KRAS gene mutation (c.35G > T/p.G12V in exon 2) in the papillary renal neoplasm with reverse polarity, with PIK3CA gene mutation restricted to the clear cell renal cell carcinoma (c.1624G > A/p.E542K in exon 10). Conclusions We report here an extraordinarily rare case of synchronous renal tumors of papillary renal neoplasm with reverse polarity and clear cell renal cell carcinoma. We identified simultaneous KRAS and PIK3CA mutations in two different renal masses in the same kidney for the first time. New pathologic assessment with comparative molecular analysis of mutational profiles may be helpful for tumor studies.

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“…7 In 2019, Al-Obaidy et al conducted a systematic analysis of 18 tumors, which they then went on to define as prototypical cases of papillary renal neoplasm with reverse polarity, summarizing the histologic and molecular characteristics of these tumors. 1,2 In this article, we summarized our findings from our analyses of 7 additional papillary renal neoplasm with reverse polarity cases, with our most notable finding being that all of these tumors were positive for 34βE12 expression in addition to being positive for GATA3.…”

Section: Discussionmentioning

confidence: 99%

“…In a separate study, these same authors identified RAS missense mutations in 8/10 tested papillary renal neoplasm with reverse polarity tumors using a next-generation sequencing approach. 2 Papillary renal cell carcinoma (PRCC) was first defined as a distinct cancer in 1976, 3 and it is now recognized as the second most common form of renal cancer following clear cell renal cell carcinoma (ccRCC), making up between 15% and 20% of all kidney cancer diagnoses. 4,5 Delahunt et al have previously proposed the further subclassification of PRCC into PRCC type 1 and PRCC type 2.…”

Section: Introductionmentioning

confidence: 99%

Papillary Renal Neoplasm With Reverse Polarity: A Clinicopathologic Study of 7 Cases

Zhou

Wang³

et al. 2020

Int J Surg Pathol

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Papillary renal neoplasm with reverse polarity is a form of recently described tumor. These tumors are defined by GATA3 positivity, negative vimentin staining, and the presence of both papillary structures and a layer of eosinophilic cells with apical nuclei and a granular cytoplasm. In the present report, we review 7 cases of papillary renal neoplasm with reverse polarity that were GATA3+ and vimentin−, consistent with past reports. In all 7 of these cases, we found that these tumors were additionally positive for 34βE12. All 7 of these tumors were categorized as stage pT1. On histological examination, these tumors exhibited branching papillae with apical nuclei. All 7 of these patients were alive on most recent follow-up, with 6 being disease free and one having developed prostate cancer. Together, this overview of 7 additional cases of papillary renal neoplasm with reverse polarity offers further insight into this rare and poorly understood disease.

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Recurrent KRAS mutations in papillary renal neoplasm with reverse polarity

Cited by 52 publications

References 25 publications

Frequent KRAS mutations in oncocytic papillary renal neoplasm with inverted nuclei

Frequent KRAS mutations in oncocytic papillary renal neoplasm with inverted nuclei

Unilateral synchronous papillary renal neoplasm with reverse polarity and clear cell renal cell carcinoma: a case report with KRAS and PIK3CA mutations

Papillary Renal Neoplasm With Reverse Polarity: A Clinicopathologic Study of 7 Cases

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