e120 P21 / British Journal of Oral and Maxillofacial Surgery 52 (2014) e75–e127

P132

Oral epithelial dysplasia: the role of ATR-Fanconianaemia pathway in malignant transformation

Michael Ho ∗, A. Triantafyllou, J.M. Risk, R.J. Shaw, J.B.Wilson

University of Liverpool

Background: The Fanconi Anaemia (FA) pathway isresponsible for homologous recombination repair of DNAinterstrand crosslink damage. This checkpoint in S-phaseof the cell cycle is mediated by ATR (Ataxia Telangiecta-sia Rad-3) and BRCA-1. The role of this tumour suppressorpathway in early oncogenesis is evaluated in oral dysplasia(OED) which transformed into oral squamous cell carcinoma(OSCC) by evaluating expression of FANC-D2 protein.

Methods: Forty patients with OED (and documented clin-ical outcomes/parameters) were identified from a cohort ofpatients who were prospectively recruited into a molecularbiomarker study (1996-2012). The OED in 23 patients trans-formed into OSCC while the remaining 17 patients were inremission. Archival formalin fixed paraffin embedded (FFPE)blocks from the first biopsy confirming the diagnosis of OED,immediately preceding malignant transformation and OSCCblocks, where applicable, were retrieved. 0.4 micron thick-ness sections were stained with FANC-D2, ATR and H2AX(control) antibodies. Immunohistochemistry (IHC) scoringwas performed by two clinicians, assessing nuclear and cyto-plasmic staining extent and intensity. Corresponding FFPEcores (0.5 mm diameter) were processed for protein and DNAextraction to validate the IHC findings.

Results: Based on the FANC-D2 dysplasia scoringsystem devised: a score ≥4 was associated with stable non-transforming OED (16 non-transformers vs. 5 transformers)and a score of ≤3 was associated with malignant transforma-tion of OED (7 non-transformers vs. 12 transformers) (Fisherexact test p = 0.02). ATR IHC showed staining patterns whichcorrelate with FANC-D2 expression. The findings of IHCwere validated with Western blots of protein extracts fromthe FFPE cores stained with FANC-D2 antibodies.

Conclusion: Failure to activate the FA pathway (indicatedby poor expression of FANC-D2 protein) due to defectiveDNA damage detection by ATR has been shown to be relatedto malignant transformation in OED. FANC-D2 IHC hasthe potential to influence the management of OED whereequipoise exists.

http://dx.doi.org/10.1016/j.bjoms.2014.07.234

P133

MD by portfolio or published work in OMFS

Barry O’Regan ∗, Rian O’Regan

Victoria Hospital, Kirkcaldy, Fife, Scotland

Introduction: The completion of a higher degree inOMFS is difficult and the window of opportunity is nar-row because of dual qualification requirements at an earlycareer stage. Many clinicians remain research motivated butare unable to commit to the timescale and demanding require-ments of a conventional research programme. Some UKMedical Schools1 currently offer an MD by portfolio of pub-lished work of “sufficient quality and academic standard” inpeer-reviewed journals1.

Aims: To compile a portfolio of theme-linked peerreviewed publications.

To develop a linking hypothesis and “uniting theme” inpersonally published material by examining postoperativecomplication rates for submission as the academic core ofan MD thesis to St Andrews University Medical School.

Method: Ten personal BJOMS publications in 6-yearperiod (2006-12) relating to two surgical techniques (retro-grade facial nerve dissection in parotidectomy and Le Fort 1tuberosity osteotomy) were chosen.

The complication rates for both techniques were comparedagainst those published for conventional methods of surgicalmanagement in the literature.

A theme related hypothesis outline entitled “An explo-ration of alternative surgical techniques in salivary glandand facial deformity surgery” was compiled, submitted andprovisionally accepted.

Results: The thesis construction roadmap and potentialpitfalls are explored. Following completion over 2 years(2011-13), an MD thesis by portfolio was successfully sub-mitted for internal and externally chosen specialty expertacademic examination.

Conclusion: The development of a portfolio of originalpublished work in peer-reviewed journals provides an encour-aging and alternative route to a higher research degree inOMFS.

Reference

1. www.st-andrews.ac.uk.

http://dx.doi.org/10.1016/j.bjoms.2014.07.235