VHL Mutation, VHL Methylation, Chromosome 3p and Whole Genomic Status in Clear Cell Papillary Renal Cell Carcinoma
Guido Martignoni, Matteo Brunelli, Diego Segala, Ioana Borze, Lilit Atanesya, Suvi Savola, Luisa Barzon, Giulia Masi, Regina Tardanico, John Nelson Eble, Marco Chilosi, Tom Bohling, Liang Cheng, Brett Delahunt, Stefano Gobbo, Sakari Knuutila. University of Verona, Verona, Italy; Hartmann Institute and HUSLab, University of Helsinki, Helsinki, Finland; MRC-Holland, Amsterdam, Netherlands; University of Padua, Padua, Italy; Spedali Civili, Brescia, Italy; Indiana University School of Medicine, Indianapolis, IN; Wellington School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand
Background: Clear cell papillary renal cell carcinoma is a renal neoplasm recently described that have to be differentiated from conventional clear cell renal cell carcinoma. We evaluated the immune- and molecular profile of a miniseries.
Design: Five clear cell papillary renal cell carcinomas were recruited only on the basis of morphological features. We analyzed the immunoexpression of cytokeratin 7 (CK7), CD10, K903, AE1/AE3, alpha-methylacyl-CoA racemase (P504S), parvalbumin, S100A1, HMB45 and Cathepsin K. Then we performed Fluorescence In Situ Hybridization (FISH) analysis by using probes for the chromosome 3 and 3p25, array Comparative Genomic Hybridization (aCGH), VHL sequencing analysis and Methylation-Specific Multiplex Ligation-dependent Probe Amplification (MS–MLPA) analysis.
Results: All neoplasms showed thick encapsulation and a tubular, tubulopapillary, tubulocystic morphology; the neoplastic cells had clear cytoplasm with low grade nuclei aligned circumferentially. All cases were positive for CK7, CD10 and AE1-AE3 and negative for P504S, parvalbumin, HMB45 and cathepsin K; all cases except one (Case 1) immunoexpress K903, whereas 3 out of 5 cases were positive for S100A1. Deletion of chromosome 3/3p by FISH, significant VHL methylation or changes in copy number by MS–MLPA and aCGH were not detected in any cases. Only one tumor (Case 1) showed VHL mutation and presented deletions of chromosome 3p and 6 at aCGH analysis.
Conclusions: We concluded that clear cell papillary renal cell carcinoma: 1) show positivity for CK7 and K903; 2) do not show 3p deletion, VHL mutation and methylation abnormalities; 3) show a genomic stability after wide whole aCGH genomic analysis. The presence of a single case with classical morphology and diffuse CK7 positivity, but with chromosome 3p deletion and VHL mutation remind to request the molecular assessment to rule out a conventional clear cell renal cell carcinoma.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 191, Tuesday Afternoon