Malignant papillary renal tumors with extensive clear cell change: A molecular analysis by microsatellite analysis and fluorescence in situ hybridization

Mohamed E. Salama, M. J. Worsham, M. DePeralta-Venturina

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Context. - Histologic subtyping of renal cell carcinomas (RCCs) is based not only on cytoarchitectural pattern but also on distinct cytogenetic abnormalities. Some renal tumors demonstrate overlapping morphologic features, rendering histologic subtyping difficult. One such group of tumors is papillary renal neoplasms with extensive clear cell change. Because histologic subtyping has been shown to be of prognostic value, it is important that malignant epithelial renal tumors be accurately subtyped. It is not known if these tumors should be classified as papillary RCC (PRCC) or as conventional/(clear cell) RCC (CRCC). Objective. - To ascertain if this subgroup of renal neoplasms demonstrates the cytogenetic abnormalities seen typically in PRCC, that is, trisomy 7 and 17 or CRCC, that is, loss of 3p, using microsatellite analysis for loss of heterozygosity (LOH), and fluorescence in situ hybridization (FISH) for trisomies. Design. - Seven RCCs from 6 patients that showed more than 75% papillary architecture and more than 75% clear cell change were included in the study. Tumor size ranged from 2.5 to 7.0 cm (mean 4.7 cm) and all were confined to the kidney (stage I). DNA was extracted from formalin-fixed paraffin-embedded tissue. FISH was done using In Situ Kits for centromere probes for chromosomes 7 and 17. For LOH, microsatellite analysis using labeled primers for 4 markers in the 3p13 through 3p24.2 region were used. The amplified polymerase chain reaction products were analyzed using an automated DNA sequencer. As compared with normal DNA, LOH in tumor was recognized as a loss of 1 allele, and microsatellite instability as the addition of an extra allele. Results. - LOH in at least 1 of the markers spanning for 3pl3 through 3p24.2 was detected in 6 of 7 specimens (86%), of which 1 also showed concomitant microsatellite instability. FISH did not demonstrate trisomy for either chromosome 7 or 17. Instead, monosomy 7 was observed in 4 of 6 tumors (67%) and monosomy 17 in all tumors (100%). Conclusion. - Because malignant papillary renal tumors with extensive clear cell change show molecular changes identical to CRCC, this subgroup of tumors may have to be classified as CRCC. This study underscores the utility of molecular studies in refining light-microscopic criteria in accurate histologic subtyping of RCCs.

Original languageEnglish (US)
Pages (from-to)1176-1181
Number of pages6
JournalArchives of Pathology and Laboratory Medicine
Volume127
Issue number9
StatePublished - Sep 1 2003

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology

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