Dysplasia grading is widely used to assess risk of transformation in oral potentially malignant disorders despite limited data on predictive value. DNA ploidy analysis has been proposed as an alternative. This study examines the prognostic value for both tests used in a routine diagnostic setting to inform clinical management. A retrospective study of conventional dysplasia grading was conducted on 1,401 patients. DNA ploidy analysis was conducted on a subset of 273 patients and results correlated with clinical information, pathologic diagnosis, and outcome over 5 to 15 years.Malignant transformation occurred in 32 of 273 patients (12%) and, of these, 20 (63%) of preexisting index lesions were aneuploid. Of 241 patients not developing carcinoma, only 39 (16%) of index lesions were aneuploid. Epithelial dysplasia correlated with DNA ploidy status (P < 0.001). The overall positive predictive value for malignant transformation by DNA aneuploidy was 38.5% (sensitivity 65.2% and specificity 75%) and by severe dysplasia grade 39.5% (sensitivity 30% and specificity 98%). DNA diploid and tetraploid status had negative predictive value of 90% to 96%. Combining DNA ploidy analysis with dysplasia grading gives a higher predictive value than either technique alone.Each of three traditional dysplasia grades predicts a significantly different risk of carcinoma development and time to transformation. DNA ploidy analysis had equivalent predictive value and also detected additional risk lesions in the absence of dysplasia. Cancer Prev Res; 6(8); 822-31. Ó2013 AACR.

Aims-To compare the expression of S100 protein, a-smooth muscle actin (a-SMA) and keratin 19 in odontogenic myxomas and non-odontogenic myxoid lesions. Methods-Formalin fixed, paraffin wax embedded tissue from seven odontogenic myxomas, three soft tissue myxomas, six hyperplastic myxoid dental follicles, two intramuscular myxomas, 12 cardiac myxomas, and seven normal dental follicles were examined immunocytochemically for S100 protein, a-SMA and cytokeratin 19 using the Streptavidin-biotin method. Results-A minority of odontogenic myxomas (three of seven) were positive for S100 and the staining was of moderate intensity and in all myxofibroblasts. Soft tissue myxomas, normal dental follicles, intramuscular myxomas, and most enlarged myxoid follicles were negative. In the cardiac myxomas the cells forming cords and islands were positive in approximately half (seven of 12), but the dispersed steilate myxoblasts were positive in only two cases. A population of cells in all the odontogenic myxomas and hyperplastic dental follicles contained a-SMA, but such cells were sparse in cardiac myxomas and present in only four cases. Cytokeratin 19 was present in odontogenic epithelium of odontogenic myxoma and follicles.Conclusions-A minority of odontogenic myxomas, but not other oral myxoid lesions, may express S100 protein and this could cause difficulty distinguishing myxoma from myxoid nerve sheath tumours. Sparse myofibroblastic cells occurred in all types ofmyxoma tested. The epithelium sometimes found within jaw myxomas expresses cytokeratin 19 and this is consistent with an odontogenic origin. (J7 Clin Pathol 1995;48:759-762)

The Fan1 endonuclease is required for repair of DNA interstrand cross-links (ICLs). Mutations in human Fan1 cause karyomegalic interstitial nephritis (KIN), but it is unclear whether defective ICL repair is responsible or whether Fan1 nuclease activity is relevant. We show that Fan1 nuclease-defective (Fan1 nd/nd ) mice develop a mild form of KIN. The karyomegalic nuclei from Fan1 nd/nd kidneys are polyploid, and fibroblasts from Fan1 nd/nd mice become polyploid upon ICL induction, suggesting that defective ICL repair causes karyomegaly. Thus, Fan1 nuclease activity promotes ICL repair in a manner that controls ploidy, a role that we show is not shared by the Fanconi anemia pathway or the Slx4-Slx1 nuclease also involved in ICL repair.

The origin of the stromal, stellate and multinucleate cells in oral giant cell fibroma is unclear. Sixteen giant cell fibromas were stained immunocytochemically for keratin (MNF 116), vimentin, S-100 protein, neurofilaments, glial fibrillary acidic protein, alpha-smooth muscle actin, desmin, CD31 (PECAM-1), CD68, Factor XIIIa and prolyl 4-hydroxylase (5B5). In all cases positive staining was found with vimentin and prolyl 4-hydroxylase, indicating a functional fibroblast phenotype. Reactivity for Factor XIIIa was seen in two cases and in only one was a small number of giant cells stained, suggesting that the majority of oral giant cell fibromas are unrelated to the histologically similar fibrous papule of the nose or facial angiofibroma.