been reported to range from 0% to 56%. The surgicaloptions employed have ranged from: decompression,marsupialization, enucleation, enucleation and curet-tage, enucleation and adjuvant treatment with cryother-apy or Carnoy’s solution, and resection. This study aimwas to evaluate the recurrence rated between two es-tablished treatment modalities: decompression followedby enucleation vs. resection or enucleation and periph-eral ostectomy with regards to recurrences.

Materials and Methods: A retrospective chart reviewof the all odontogenic keratocysts treated in the depart-ment of Oral and Maxillofacial Surgery at the Universityof Maryland from 1998 to 2004 was undertaken. Thissearch identified 31 patients. A total of 9 patients wereexcluded either due to inadequate follow-up or becausethey were syndromic patients. The patients were thendivided into two treatment groups. Group I consisted ofpatients treated with resection or enucleation and pe-ripheral ostectomy. Group II consisted of patientstreated with decompression followed by enucleation.Using the clinical and radiographic data from the clinicalcharts, demographic, treatment and recurrence datawere then extracted.

Method of Data Analysis: Retrospective chart review,comparative analysis of data.

Results: A total of 22 patients with biopsy provenOKCs met the inclusion criteria. Their age ranged from18 to 90 years old. Two treatment arms were thenformed, resection or enucleation and peripheral ostec-tomy (Group I) and decompression followed by enucle-ation (Group II). Group I consisted of 11 patients, 6females and 5 males. Six OKCs were located in themandible and 5 in the maxilla. Their age ranged from 18to 71 years. Group II consisted of 11 patients, 6 femalesand 5 males. Their age ranged from 24 to 90 years. Tenpatients had OKCs in the mandible and 1 in the maxilla.The choice of resection/peripheral ostectomy vs. de-compression was based on the size of the cyst (�2 cm),recurrence status, and/or radiographic evidence of cor-tical perforation. Follow-up ranged from 1 to 9 years forgroup I and from 1 to 3 years for group II. There were norecurrences at last follow up for patients in group I (0%)while in group II there were two recurrences (18%). Thepatients who recurred in group II had a repeat enucle-ation and peripheral ostectomy and were without evi-dence of disease at last follow-up.

Conclusion: The results from this retrospective studyshow that both modalities are adequate therapeutic op-tions for the treatment of the odontogenic keratocysts.Although the patients treated in group II had a recur-rence rate compared to the resected/peripheral ostec-tomy group, the morbidity was far less. We have adoptedthe practice of decompression of large OKCs followedby enucleation thus obviating the need for more aggres-sive surgery.

References

Brannon RB: The odontogenic keratocyst. A clinicopathologic studyof 312 cases. Part I. Clinical features. Oral Surg Oral Med Oral Pathol.42:54, 1976

Brannon RB: The odontogenic keratocyst. A clinicopathologic studyof 312 cases. Part II. Histologic features. Oral Surg Oral Med Oral Pathol43:233, 1977

Large Scale Genome Wide MolecularProfiling in Oral CancerVictor Lopes, FRCS, FDSRCS, Department ofMaxillofacial Surgery, University Hospital BirminghamNHS Trust, Edgbaston, Birmingham, West MidlandsB15 2TH, UK (Wei WB; Murray P)

Statement of the Problem: Many attempts have beenmade to improve the classification of sub-groups of oralcancer. Traditional attempts to define such groups haveused histological features and various molecular markersas well as clinical features such as nodal status. All suchattempts have provided only limited improvements intumor taxonomy and disease prognostication. The ad-vent of microarray technology has led to great advancesin disease taxonomy in other tumor types includingbreast cancer, B-cell lymphoma, and melanoma. Geneexpression arrays have also provided an insight into themost important genes involved in tumor metastasis.Gene expression patterns have also been defined inseveral studies of oral cancer. Sub-groups of tumourshave been defined by such studies and particular impor-tance has been given to trying to define the clinicalcorrelates of such groups. However, this has not been asclearly demonstrated as in breast cancer and B-cell lym-phoma. Furthermore, there have been no genome widestudies of chromosomal imbalances published to daterelating to oral cancer.

Materials and Methods: In this study we comparedtwo cohorts of patients with oral cancer from the UnitedKingdom and Sri Lanka. In the UK and USA oral cancerforms around 4% of all cancers whereas in Sri Lanka, oralcancer is the single most common tumor forming 35% ofall cancers. In each case the risk factors for developingoral cancer are very different. In the UK the main riskfactor is tobacco smoking; however, in Sri Lanka thepredominant risk factor is Betel Quid chewing. In ourstudy we have examined genome wide chromosomalimbalances in a sequential series of 30 oral cancersobtained from a single centre in the United Kingdom.These were then compared to a sequential series of 30oral cancers obtained from Sri Lanka. In both series wealso examined gene expression profiles. In each samplechromosomal imbalances were mapped onto gene ex-pression levels. Gene expression patterns were derivedusing the Affymetrix focus array and a number of bioin-formatics software applications. Chromosomal imbal-ances were analysed using the Affymetrix Single Nucle-

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otide Polymorphism (SNP) array and GDAS software.Both RNA and DNA were extracted from each tumor.

Method of Data Analysis: Software packages: GCOS,GDAS, RMA, SAM.

Results: Our work demonstrates clear patterns of chro-mosomal imbalances and gene expression profiles asso-ciated with both UK and Sri Lankan oral cancer and thatthese are grossly different. Within each cohort sub-groups can be defined on the basis of gene expressionpatterns and close correlations are drawn with clinicalfeatures of the tumors. We shall also demonstrate howchromosomal imbalances appear to have an effect ongene expression patterns and that these are unique toeach cohort.

Conclusion: This work clearly demonstrates uniquepatterns of chromosomal imbalance and gene expres-sion associated with oral cancer arising from two distinctaetiological groups. Furthermore these patterns can becorrelated to the clinical course of the disease.

References

Alizadeh AA, et al: Nature 403:503, 2000Nagata M, et al: Int J Cancer 106:683, 2003O’Donnell R, et al: Oncogene online 2004 doi:10.1038/sj.onc.208285

Gene Expression Changes in Response toTherapeutic Doses of Irradiation andMolecular Manipulation to Change SuchResponses in an Oral Cancer Cell LineVictor Lopes, FRCS, FDSRCS, Department ofMaxillofacial Surgery, University Hospital BirminghamNHS Trust, Edgbaston, Birmingham, West MidlandsB15 2TH, UK (Offer N; Wei WB; Murray P)

Statement of the Problem: Investigating the effects ofionising radiation on cells cultured in-vitro has alwaysbeen difficult because of concerns regarding dosimetry.Frequently investigators have been forced to use gammasources and have assumed 100% dose absorption. Wehave developed a protocol that simulates a biologicalsystem and is carefully dose controlled. This system willallow adherent oral cancer cell lines to be irradiated in amanner similar to a tumor within the body. As a result itis possible to study genome wide gene expressionchanges in oral cancer cell lines; about which to datelittle is understood.

Materials and Methods: We examined the gene expres-sion changes in the oral cancer cell line SCC4 at 3, 6, and12 hours post-irradiation with gamma rays. Therapeuticdoses of irradiation (2-4 Gy) were used in a single frac-tion. RNA was extracted from the cells in culture andeach irradiation was repeated 3 times. We used theAffymetrix focus array to determine gene expression ateach time point. Gene expression changes were vali-dated by RT-PCR and Western blotting.

Method of Data Analysis: Software packages GCOS,RMA, and SAM.

Results: Using therapeutic doses of radiation (2-4 Gy)we can show that the great majority of gene expressionchanges occur within the first 3 hours after irradiationand that by 12 hours there are few changes in geneexpression compared to unirradiated cells. We also dem-onstrate that a large proportion of the conventional DNAdamage response genes are not activated after a singlefraction of radiation to the p53 mutant cell line SCC4.However we are able to demonstrate a dramatic upregu-lation of one of the cohesin sub-units which is respon-sible for homologous recombination (DNA repair). Wehave also shown that this same gene is not upregulatedin p53 wild type cell lines in response to irradiation butis upregulated in a proportion of ex-vivo irradiated pri-mary oral cancers. We shall also present data showingthat manipulation of the expression of this gene canhave effects on the cell dramatically changing the re-sponse of the cell to irradiation.

Conclusion: Modifying the cellular response to irradi-ation may in future prove to be a useful therapeuticintervention. In particular, amplifying cellular responsemay allow radiation dose reduction. This would be mostadvantageous when radiation is used as an adjuvant ther-apy. Here the benefits are less clear when compared topotential complications. Dose reduction would reducecomplications and improve the safety profile of adjuvantradiotherapy.

References

Birkenbihl RP, et al: Nucleic Acids Res 20:6605, 1992Zhang Y, et al: Radiat Res 161:667, 2004

Characterization of Neuropilin-1 inSquamous Cell Carcinoma of the Tongue:A Laboratory StudySanjay Sharma, BDS, MBBS, FDSRCS, MRCSI, MRCS, 5Cadgwith Place, Port Solent, Hampshire PO6 4TD, UK(Quintera-Ortiz M; Spedding A; Anand R; Faris K;Brennan P; Cree I)

Statement of the Problem: Angiogenesis is a key pro-cess in the growth of all solid tumors. Neuropilin-1 hasrecently been identified as a co-receptor for vascularendothelial growth factor receptor 2 (VEGFR2) and en-hances the binding of VEGF-165 to VEGFR2 promotingendothelial cell proliferation. Neuropilin-1 has been de-scribed in breast, prostate, and lung cancers. We aim tocharacterize neuropilin-1 in squamous cell carcinoma.

Materials and Methods: Immunohistochemical stain-ing of 38 paraffin fixed sections of primary tongue squa-mous cell carcinoma (SCC) with antibodies to NRP-1,VEGF-165, and CD34. Real-time quantitative polymerasechain reaction (RT-qPCR) and Western blots of SCC celllines for mRNA and protein respectively.

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40 AAOMS • 2005