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PROGNOSTIC CLASSIFIER FOR ORAL POTENTIALLY MALIGNANT DISORDERS: AN
INTEGRATED HISTOPATHOLOGICAL AND MOLECULAR APPROACH

Hans Prakash S, Philip Sloan, Ralf Kist, Max Robinson

Introduction: Oral squamous cell carcinoma (OSCC) is associated with a high degree of
morbidity and mortality. OSCCs are often preceded by oral potentially malignant disorders
(OPMD) which have a higher propensity to undergo malignant transformation (MT)
compared to clinically normal oral mucosa. Currently there is no reliable method to
determine which OPMD cases will undergo MT. Objectives: This study was performed to
construct a prognostic classifier for patients with OPMD by integrating clinical,
histopathological and molecular factors and to discover a gene expression signature that
characterises OPMD with a high risk of undergoing MT. Results: Statistical analysis of an
OPMD patient cohort (23 MT vs. 25 with no MT) showed that site of initial OPMD
(p = 0.043), binary oral epithelial dysplasia (OED) grading (p = 0.009) and loss of
heterozygosity at 3p/9p/17p (p = 0.026) were statistically significant. Other demographic
factors, clinical features and the WHO 3-tiered OED grading system were not statistically
significant. Gene expression experiments revealed several genes that were differentially
expressed between OPMD that underwent MT and those that did not [false discovery rate
of < 0.05]. Statistical model building was performed, and the outputs were used to
construct a prognostic classifier. Conclusions: A classifier combining histopathological and
molecular factors outperforms conventional methods for prognosticating clinical outcome
in patients with OPMD and formalin-fixed paraffin-embedded tissue can be used to
generate a molecular classification with clinical utility.

Published in Journal of Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 128, Issue 1, 2019

Dr Hans P Sathasivam
Centre for Oral Health Research
Newcastle University, UK
Institute for Medical Research
NIH Malaysia

Prof Dr Philip Sloan
Dr Max Robinson
Centre for Oral Health Research
Department of Cellular Pathology
Newcastle University UK

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