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Toxicologic Pathology
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Articles

Histological Investigation of Diagnostically Challenging Tubule Profiles in Advanced Chronic Progressive Nephropathy (CPN) in the Fischer 344 RaT

Gordon C. Hard1
John Curtis Seely2

1 Consultant, National Toxicology Program Archives, Research Triangle Park, North Carolina 27709, USA
2 Experimental Pathology Laboratories Inc., Research Triangle Park, North Carolina 27709, USA

Correspondence: Address correspondence to: John Seely, Experimental Pathology Laboratories, Research Triangle Park, NC 27709, USA; e-mail:jseely{at}eplinc.com

Recently, guidelines were suggested for discriminating proliferative-appearing tubule profiles encountered in advanced spontaneous chronic progressive nephropathy (CPN) of rats, from hyperplastic precursors of renal tubule tumors (Hard and Seely, 2005). These recommendations were based on histological evaluation of a large number of cases of severe to end-stage CPN in male F344 rats from 8 separate 2-year carcinogenicity studies held in the Archives of the National Toxicology Program, NIEHS. This work has now been extended to characterize the various lesions further, mainly by serial sectioning to track their origin and fate within the adjacent renal tissue, but also by applying special staining procedures such as immunohistochemical assessment of proliferative activity, as well as fluorescence microscopy, to seek further differences from atypical tubule hyperplasia. The results obtained from these additional investigations support the contention that certain tubule profiles with a misleading proliferative appearance, sometimes found in advanced CPN, should be distinguished from preneoplastic tubule foci, and regarded as components of the nephropathy process.

Key Words: CPN • proliferative tubule profiles • atypical tubule hyperplasia • special stains • serial-sectioning

Abbreviations: ATH, atypical tubule hyperplasia • CPN, chronic progressive nephropathy • NTP, National Toxicology Program • PAS, periodic acid Schiff reagent • PCNA, proliferating cell nuclear antigen

Toxicologic Pathology, Vol. 34, No. 7, 941-948 (2006)
DOI: 10.1080/01926230601083381
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