Survivin, cyclin D1, and p21hras in keratocystic odontogenic tumors before and after decompression.

OBJECTIVES: 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. MATERIALS AND METHODS: We analyzed eighteen keratocystic tumors treated by decompression and subsequent enucleation along with seven pericoronal follicles using immunohistochemistry. RESULTS: 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. CONCLUSIONS: 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.

Somatic genomic imbalances in 'tumour-free' surgical margins of oral cancer.

Up to 30% of oral squamous cell carcinoma (OSCC) patients develop local recurrence and distant metastasis. The molecular status of histologically cancer-free tumour margins could be a critical factor in predicting tumour behaviour. The aim of this study was to detect somatic genomic imbalances in OSCC with emphasis on the surgical margins. DNA was isolated from tumour tissues, margin tissues, and blood samples (used as control) obtained from 11 OSCC patients, and genome-wide array comparative genomic hybridization was performed. Imbalances were present in both tumours and margins, although, as expected, they were more prevalent in tumours (duplications, P = 0.0002; deletions, P = 0.0001). Duplications were more frequent than deletions in both tumours and margins, but without statistical significance. Fifteen imbalances in tumour tissues were recurrent and all of them were duplications. Four of these were found both in tumours and margins and involved chromosomes 1q, 8p, Xp, Yp, and Yq. Four imbalances were recurrent in margin tissue and all of them were duplications (autosomes 8 and 17 and both sex chromosomes). Histologically 'cancer-free' margins hide genomic alterations consistent with unexplained OSCC recurrences. Establishing the molecular status of the margins could improve outcome prediction.

Bcl-2 expression in oral squamous cell carcinoma.

Apoptosis is a genetically regulated process involved in tissue size regulation, morphogenesis, and elimination of genetically damaged cells. A pallet of genes is involved in the control of apoptosis, such as bcl-2 family whose oncogenic potential has been demonstrated in oral tumorigenesis. Different members of bcl-2 family may promote or inhibit apoptosis by synthesizing anti- and proapoptotic proteins. One of antiapoptotic proteins, bcl-2, with a crucial role in apoptosis regulation was the object of our study. By means of immunohistochemistry we estimated the level of overexpression of bcl-2 proteins in a series of the 26 formalin fixed, paraffin-embedded samples of oral squamous cell carcinoma (OSCC). Analyzed tumors originated from different sites of oral cavity; 7/26 belonged to stage II, 14/26 to stage III, and 5/26 to stage IV. Immunoreactivity was scored according to the percentage and intensity of positive cytoplasmic bcl-2 staining. All tumors had low percentage of positively stained bcl-2 cells, with mean values for lower/higher intensity of 8.3 +/- 2.5/34.4 +/- 7, 7.5 +/- 1.1/31.9 +/- 4.3, and 8.4 +/- 5.8/31.5 +/- 5.8 within stages II, III, and IV, respectively. Low level of bcl-2 expression in our sample seems to be associated with higher survival rate: 77% for the 5-year follow-up period. Comparing clinicopathologic and risk factors data within each and between three groups of analyzed tumors (lip-tongue P = 0.58, tongue-floor of the mouth, P = 0.21, lip-floor of the mouth, P = 0.50) there was no significant difference. However, our results suggest that the level of bcl-2 expression could be a valuable predictor of tumor behavior and disease outcome.

The amplification of c-erb-B2 in cancer-free surgical margins is a predictor of poor outcome in oral squamous cell carcinoma.

The tumour subtype, TNM classification, and histopathological data are sometimes not sufficient for understanding and assessing the behaviour of oral cancers. In an attempt to find additional markers of tumour biology and behaviour, this study sought to determine the incidence and consequently the relevance of c-erb-B2, c-Myc, and H-ras gene alterations in tumour-free margins of oral squamous cell carcinoma (OSCC). Fifty samples of OSCC were analyzed for c-erb-B2 and c-Myc amplification by real-time polymerase chain reaction and for H-ras point mutations by sequencing. A relatively high incidence of genetic lesions was detected: 22% of cases had c-erb-B2 and 30% had c-Myc amplification, whilst only 12% harboured H-ras mutations. Kaplan-Meier analysis and the log-rank test showed statistically significant differences in 5-year survival rates and relapse between patients with tumour margins positive for c-erb-B2 amplification and those with margins that were negative (P=0.002). H-ras and c-Myc alterations could not be associated with tumour behaviour. Molecular analysis of margins, targeting cancer genes, could identify additional, independent predictors of risk and outcome in OSCC.