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Recurrent KRAS mutations identified in papillary renal neoplasm with reverse polarity—a comparative study with papillary renal cell carcinoma
- Source :
- Modern Pathology. 33:690-699
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Comprehensive molecular analyses revealed that papillary renal cell carcinoma (PRCC) is a heterogenous entity. Papillary renal neoplasm with reverse polarity (PRNRP) is a subset of PRCC with characteristic histomorphologies such as low-grade nuclear features, inverted nuclear location, eosinophilic cytoplasm, and indolent clinical behavior. We tried to define the molecular, clinicopathological, histologic, and immunohistochemical features of PRNRP by comparing them with type 1 PRCC (PRCC1) and type 2 PRCC (PRCC2). A cohort of 30 PRNRP, 23 PRCC1, and 26 PRCC2 cases was used. Targeted sequencing of 90 cancer-related genes including KRAS was performed in 26 PRNRP tumor samples. PNA-mediated clamping PCR of KRAS was performed using paired normal and tumor DNA from 30 PRNRP, 23 PRCC1, and 26 PRCC2 cases. Tissue microarray slides were made in three cores per tumor, which were stained with cytokeratin 7 (CK7), alpha-methylacyl-CoA racemase (AMACR), epithelial membrane antigen (EMA), E-cadherin, vimentin, and CD10. Recurrent mutations in KRAS were detected in 28 of the 30 PRNRPs. However, there were no KRAS mutations in any PRCC1 or PRCC2 cases. PRNRP exhibited distinct clinicopathological features: small tumor size, lower pathologic T stage, and no disease-specific death during the follow-up period. Histologically, peritumoral lymphoid aggregation, prominent papillary architecture (>80% of tumor), hyalinized papillae, inverted nuclear location, and lower nuclear grade were observed. PRNRP was usually positive for CK7, AMACR, EMA, and E-cadherin, and negative for CD10. The findings suggest that PRNRP is a subtype of papillary renal neoplasm that is different from PRCC1 or PRCC2 in terms of molecular, clinicopathological, histological, and immunohistochemical features.
- Subjects :
- Male
0301 basic medicine
Pathology
medicine.medical_specialty
DNA Mutational Analysis
Vimentin
Biology
medicine.disease_cause
Pathology and Forensic Medicine
Renal neoplasm
Proto-Oncogene Proteins p21(ras)
03 medical and health sciences
Cytokeratin
0302 clinical medicine
Republic of Korea
Biomarkers, Tumor
medicine
Humans
Genetic Predisposition to Disease
Carcinoma, Renal Cell
Aged
Neoplasm Staging
Tissue microarray
Papillary renal cell carcinomas
Middle Aged
Immunohistochemistry
Kidney Neoplasms
Tumor Burden
Phenotype
030104 developmental biology
030220 oncology & carcinogenesis
Mutation
biology.protein
T-stage
Female
KRAS
Subjects
Details
- ISSN :
- 08933952
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- Modern Pathology
- Accession number :
- edsair.doi.dedup.....27d4c3e34e32672eca740080396fdbb7