A reproducible and simple grading system for classical chondrosarcomas. Analysis of 35 chondrosarcomas and 16 enchondromas with emphasis on recurrence rate and radiological and clinical data.

In the past, six histological grading systems for classical chondrosarcoma have been published. Due to the inhomogeneity and complexity of these classifications, the comparison of clinical data, survival rates and local failures has to be considered critically. In 1996, the author published a grading system that was simple to use and easily reproduced. This system was based on a few nuclear features. The main intention of the current study was to verify whether the histological grade, which was defined by the author's classification, correlates with the recurrence rate. In a retrospective study, clinical data, X-rays and histological material from 35 patients with classical chondrosarcoma and 16 patients with enchondroma were analysed. Statistical analysis was done using the chi-squared test and the Fisher exact test. Local recurrence occurred in 25.7% of all patients. The difference in recurrence rate among grades 1-3 was statistically significant ( P=0.002). The frequency of grades 1-3 varied up to 54%, when published grading systems were compared. No significant difference between the histological grade and features such as double nuclei and mitosis were observed. The frequency of cellularity, double nuclei and mitoses was similar between enchondromas and low-grade chondrosarcomas. Of chondrosarcoma patients, 90.6% of total patients and 87.5% of those with grade-1 lesions reported pain, whereas only 43.8% of the enchondroma patients did. Even in patients with grade-1 chondrosarcomas, radiological findings were much more aggressive in comparison with enchondromas. The histological grade, defined on the basis of the author's simple and reproducible grading system, indicates the risk of local recurrence, especially in cases that are inadequately treated. Grade-3 chondrosarcomas and lesions located in regions where the removal of the tumour would be difficult have to be given special attention.

Characterization of a major modifier locus for polycystic kidney disease (Modpkdr1) in the Han:SPRD(cy/+) rat in a region conserved with a mouse modifier locus for Alport syndrome.

The genetic analysis of rodent disease models provides a powerful tool to investigate how modifier loci cause variation in the phenotypic expression of a disease. In order to test the existence of modifier loci influencing polycystic kidney disease (PKD) phenotypes, we derived a backcross between PKD susceptible Han:SPRD(cy/+) and control Brown Norway (BN) rats, and performed a whole-genome scan in 182 PKD affected hybrids showing different grades of disease severity. The genetic dissection of PKD in the cross allowed us to detect a modifier locus, Modpkdr1, on rat chromosome 8 that controls PKD severity, kidney mass and plasma urea concentration. Results from database searches and computational analyses demonstrated that the Modpkdr1 locus shows strong evidence of synteny conservation with human and mouse chromosomal regions controlling kidney diseases, including disease progression of Alport syndrome. Comparative genome mapping also provided an inventory of potential candidate genes for modifier(s) of PKD. Analyses of the coding regions for four strong candidates (Ctsh, Bcl2a1, Trpc1 and Slc21a2) in (cy/+), BN and Lewis rat strains did not reveal sequence variants that could be associated with PKD. The characterization of Modpkdr1 may provide new insights into modulating mechanisms involved in the pathogenesis of PKD that could delay disease progression in humans. It may also have strong implications in the identification of pathophysiological factors common to different renal disorders.