1. Recurrent KRAS mutations identified in papillary renal neoplasm with reverse polarity—a comparative study with papillary renal cell carcinoma
- Author
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Keun Hong Kee, Chan Choi, Kyoung Min Kim, Sung Sun Kim, Jo-Heon Kim, Yong Mee Cho, Hun-Soo Kim, and Gi Hwan Kim
- 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 - 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.
- Published
- 2020