cyclin-d1 and Jaw-Diseases

The aim of the present study was to analyze the expression levels of Cyclin D1 (CCD1), a nuclear protein that plays a crucial role in cell cycle progression, in a series of keratin-producing odontogenic cysts.. A total of 58 keratin-producing odontogenic cysts, diagnosed over ten years and classified according to the WHO 2005 criteria, were immunohistochemically analyzed in terms of CCD1 expression, which was quantified in the basal, suprabasal and intermediate/superficial epithelial compartments. The extent of immunostaining was measured as a proportion of total epithelial thickness. Quantified immunohistochemical data were correlated with clinicopathological features and clinical recurrence.. Keratin-producing odontogenic cysts were classified as 6 syndromic keratocystic odontogenic tumors (S-KCOT), 40 sporadic or non-syndromic KCOT (NS-KCOT) and 12 orthokeratinized odontogenic cysts (OOC). Immunohistochemically, CCD1 staining was evident predominantly in the parabasal region of all cystic lesions, but among-lesion differences were apparent, showing a clear expansion of parabasal compartment especially in the S-KCOT, followed to a lesser extent in the NS-KCOT, and being much more reduced in the OOC, which had the greatest average epithelial thickness.. The differential expression of CCD1 noted in the present study suggests that dysregulation of cell cycle progression from G1 to the S phase contributes to the different aggressiveness of these lesions. However, CCD1 expression levels did not predict NS-KCOT recurrence, which is likely influenced by factors unrelated to lesion biology.

Topics: Adult; Cyclin D1; Female; Humans; Jaw Diseases; Keratins; Male; Middle Aged; Odontogenic Cysts; Retrospective Studies

To investigate HRPT2 in jaw ossifying fibroma (OF), fibrous dysplasia (FD), and osteosarcoma (OS).. We combined microsatellite loss of heterozygosity (LOH), HRPT2 sequence alterations at the mRNA level by reverse-transcription polymerase chain reaction (PCR), cDNA sequencing, and quantitative PCR (qPCR) and immunohistochemistry (IHC) in a total of 19 OF, 15 FD, and 9 OS. Because HRPT2 (parafibromin) interacts with cyclin D1, we investigated cyclin D1 expression with the use of qPCR and IHC.. LOH was detected in 3/5 FD, 6/9 OF, and 2/2 OS heterozygous samples. LOH was not associated with decreased mRNA levels or HRPT2 protein expression except for 1 OF which harbored an inactivating mutation. However, this tumor did not display altered transcription or protein levels of HRPT2 nor cyclin compared with the other OF.. The contribution of HRPT2 inactivation to the pathogenesis of OF, FD, and OS is marginal at best and may be limited to progression rather than tumor initiation.

Topics: Adolescent; Adult; Aged; Chromosome Mapping; Chromosomes, Human, Pair 1; Cyclin D1; Disease Progression; Exons; Female; Fibroma, Ossifying; Fibrous Dysplasia of Bone; Gene Silencing; Humans; Hyperparathyroidism; Jaw Diseases; Jaw Neoplasms; Loss of Heterozygosity; Male; Microsatellite Repeats; Middle Aged; Mutation; Osteosarcoma; RNA, Messenger; Sequence Deletion; Transcription, Genetic; Tumor Suppressor Proteins; Young Adult

Several reports have demonstrated the presence of a high proliferative activity in central giant cell granuloma, raising the possibility that deregulation of the cell cycle may contribute to its pathogenesis. As we identified alterations of cyclin D1 in giant cell tumor of bone, and as there are histologic similarities between central giant cell granuloma and giant cell tumor, we assessed jaw lesions for the presence of similar alterations.. Formalin-fixed, paraffin-embedded tissue from 29 cases of central giant cell granuloma was assessed for the expression of cyclin D1, cyclin B1, and MIB-1 (Ki-67) using immunohistochemistry. In addition, differential polymerase chain reaction (PCR) was used to determine whether there was cyclin D1 gene amplification.. The cyclin D1 gene copy number appeared to be minimally elevated in 31% of the cases. Cyclin D1 protein overexpression was observed in 28 of 29 cases (96.5%). Immunostaining was present predominantly in the nuclei of the giant cells. Cyclin B1 and MIB-1 immunoreactivity was restricted to the mononuclear cells with no staining present in the giant cells.. Cyclin D1 protein overexpression may be involved in the formation of the giant cells and the pathogenesis of central giant cell granuloma. As the distribution of immunostaining is identical to that observed in giant cell tumor of bone, our results support the possibility that central giant cell granuloma of the jaws and giant cell tumor of bone represent a similar disease process that clinically and histologically may have somewhat different features because of differences in the anatomical site of involvement.

Topics: Cell Cycle Proteins; Cyclin B; Cyclin B1; Cyclin D1; Gene Expression; Granuloma, Giant Cell; Humans; Immunoenzyme Techniques; Jaw Diseases; Ki-67 Antigen; Polymerase Chain Reaction; Tumor Cells, Cultured