cyclin-d1 and Mandibular-Neoplasms

The aim of this study was to investigate survivin, cyclin D1, and p21hras expression in keratocystic odontogenic tumors before and after decompression, as well as in pericoronal follicles. A potential correlation between the expression levels of these proteins was also investigated.. We analyzed eighteen keratocystic tumors treated by decompression and subsequent enucleation along with seven pericoronal follicles using immunohistochemistry.. Keratocystic tumor samples, both before and after decompression, were positive for each of the investigated proteins. In pericoronal follicles, survivin exhibited cytoplasmic staining in contrast to nuclear staining in keratocystic tumors. Cyclin D1 expression was negative in pericoronal follicles, and p21hras expression was similar in both groups. Survivin showed significantly higher expression after decompression, while cyclin D1 and p21hras remained unchanged (P = 0.039, P = 0.255, P = 0.913, respectively). There was no correlation between these proteins neither before nor after decompression.. Within the limits of the study, we can conclude that following decompression, keratocystic odontogenic tumors preserve distinct immunohistochemical profiles of cyclin D1 and p21hras expression, despite substantial reduction in size of the lesions. Significant increase of survivin expression after decompression might be attributed to higher level of epithelial proliferation caused by this procedure.

Topics: Adolescent; Adult; Aged; Cyclin D1; Decompression, Surgical; Female; Humans; Inhibitor of Apoptosis Proteins; Male; Mandibular Neoplasms; Maxillary Neoplasms; Middle Aged; Odontogenic Cysts; Odontogenic Tumors; Proto-Oncogene Proteins p21(ras); Survivin; Young Adult

Sonic hedgehog (SHH) pathway activation has been identified as a key factor in the development of many types of tumors, including odontogenic tumors. Our study examined the expression of genes in the SHH pathway to characterize their roles in the pathogenesis of keratocystic odontogenic tumors (KOT) and ameloblastomas (AB).. We quantified the expression of SHH, SMO, PTCH1, SUFU, GLI1, CCND1, and BCL2 genes by qPCR in a total of 23 KOT, 11 AB, and three non-neoplastic oral mucosa (NNM). We also measured the expression of proteins related to this pathway (CCND1 and BCL2) by immunohistochemistry.. We observed overexpression of SMO, PTCH1, GLI1, and CCND1 genes in both KOT (23/23) and AB (11/11). However, we did not detect expression of the SHH gene in 21/23 KOT and 10/11 AB tumors. Low levels of the SUFU gene were expressed in KOT (P = 0.0199) and AB (P = 0.0127) relative to the NNM. Recurrent KOT exhibited high levels of SMO (P = 0.035), PTCH1 (P = 0.048), CCND1 (P = 0.048), and BCL2 (P = 0.045) transcripts. Using immunolabeling of CCND1, we observed no statistical difference between primary and recurrent KOT (P = 0.8815), sporadic and NBCCS-KOT (P = 0.7688), and unicystic and solid AB (P = 0.7521).. Overexpression of upstream (PTCH1 and SMO) and downstream (GLI1, CCND1 and BCL2) genes in the SHH pathway leads to the constitutive activation of this pathway in KOT and AB and may suggest a mechanism for the development of these types of tumors.

Topics: Adolescent; Adult; Ameloblastoma; Ameloblasts; Cyclin D1; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Hedgehog Proteins; Humans; Male; Mandibular Neoplasms; Middle Aged; Mouth Mucosa; Neoplasm Recurrence, Local; Odontogenic Tumors; Patched Receptors; Patched-1 Receptor; Proto-Oncogene Proteins c-bcl-2; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Repressor Proteins; Smoothened Receptor; Transcription Factors; Transcription, Genetic; Young Adult; Zinc Finger Protein GLI1

Nevoid basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominant disorder characterized by developmental abnormalities and a predisposition to cancers. Although multiple jaw tumors, such as keratocystic odontogenic tumors (KCOTs), are one of the most frequent complications in NBCCS, the molecular mechanism for how KCOTs develop in NBCCS is poorly understood. A 15-year-old girl with 2 jaw tumors was diagnosed as NBCCS according to the clinical criteria. The pathologic findings indicated that the 2 tumors were consistent with KCOTs. A PTCH1 mutation, c.1472delT, was detected in her peripheral blood as well as in the 2 tumors. Interestingly, an additional PTCH1 mutation, c.264_265insAATA, that was not present in the peripheral blood, was found in the maxillary tumor but not the mandibular tumor. The Ki-67 labeling index was significantly higher in the maxillary KCOT (17.7%) than in the mandibular KCOT (14.3%). These findings indicate distinct molecular mechanisms of tumorigenesis in these KCOTs.

Topics: Adolescent; Basal Cell Nevus Syndrome; Cyclin D1; DNA Mutational Analysis; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Mandibular Neoplasms; Maxillary Neoplasms; Odontogenic Tumors; Patched Receptors; Patched-1 Receptor; Receptors, Cell Surface

To elucidate the expression and significance of cell cycle-associated proteins in chondrosarcoma of the jaws, Cyclin Dl, CDK4, p27, E2F-l and Ets-l expressions were examined in chondrosarcoma and osteochondroma of the jaws by immunohistochemical ABC method. The results demonstrated that Cyclin Dl, CDK4, p27, E2F-1 and Ets-1 were positive 75% (15 of 20), 60% (12 of 20), 25% (5 of 20), 65% (13 of 20) and 60% (12 of 20) in chondrosarcoma of the jaws, respectively. There was no remarkable difference in the expression of these proteins among histological grades of the chondrosarcoma (P>0.05). In osteochondroma of the jaws, CDK4 and E2F with an equal positivity of 12.5% (1 of 8), whereas p27 was positive 75% (6 of 8). None of the osteochondroma cases was immunohistochemically positive for Cycin Dl and Ets-1. In addition, the positive rate of Cyclin Dl, CDK4, E2F-l and Ets-1 proteins was significantly higher, whereas p27 was lower in chondrosarcoma than in osteochondroma of the jaws (P<0.05). These data show that the expression of cell cycle regulatory proteins is altered in chondrosarcoma of the jaws: cyclin Dl, CDK4, E2F-1 and Ets-1 are over-expressed and p27 is low-expressed.

Topics: Adolescent; Adult; Cell Cycle Proteins; Chi-Square Distribution; Child; Chondrosarcoma; Cyclin D1; Cyclin-Dependent Kinases; DNA-Binding Proteins; E2F Transcription Factors; E2F1 Transcription Factor; Female; Humans; Male; Mandibular Neoplasms; Maxillary Neoplasms; Microfilament Proteins; Middle Aged; Muscle Proteins; Neoplasm Proteins; Osteochondroma; Proto-Oncogene Protein c-ets-1; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-ets; Transcription Factors