MyMedR

Displaying all 7 publications

Abstract:

Sort:

The clinical utility of contemporary oral epithelial dysplasia grading systems

Sathasivam HP, Sloan P, Thomson PJ, Robinson M

J Oral Pathol Med, 2022 Feb;51(2):180-187.
PMID: 34797585 DOI: 10.1111/jop.13262

INTRODUCTION: Clinical management of oral potentially malignant disorders relies on accurate histopathological assessment of the presence and grade of oral epithelial dysplasia. While adjunctive laboratory tests have provided useful prognostic information, none are in widespread clinical use. This study was performed to assess the clinical utility of two contemporary oral epithelial dysplasia grading systems.
METHODS: Patients were identified from a clinical database. Oral epithelial dysplasia grading was performed by three oral and maxillofacial pathologists blinded to clinical outcome using the WHO 2017 system and a binary classification. The primary outcome measure was the development of oral squamous cell carcinoma, termed 'malignant transformation'.
RESULTS: One hundred thirty-one cases satisfied the inclusion criteria, of which 23 underwent malignant transformation. There was substantial inter-rater agreement between the study pathologists for both grading systems, measured using kappa statistics (κ = 0.753 - 0.784). However, there was only moderate agreement between the consensus WHO 2017 dysplasia grade for the study against the original grade assigned by a pool of six pathologists in the context of the clinical service (κ = 0.491). Higher grade categories correlated with an increased risk of developing cancer using both grading systems.
CONCLUSION: This study demonstrates that the WHO 2017 and binary grading systems are reproducible between calibrated pathologists and that consensus reporting is likely to improve the consistency of grading. The WHO and binary systems were prognostically comparable. We recommend that institutions implement consensus oral epithelial dysplasia grading and prospectively audit the effectiveness of risk stratifying their patients with oral potentially malignant disorders. (249 words).
Dysplasia and DNA ploidy to prognosticate clinical outcome in oral potentially malignant disorders

Sathasivam HP, Nayar D, Sloan P, Thomson PJ, Odell EW, Robinson M

J Oral Pathol Med, 2021 Feb;50(2):200-209.
PMID: 33151583 DOI: 10.1111/jop.13121

BACKGROUND: Oral potentially malignant disorders are a clinical conundrum as there are no reliable methods to predict their behaviour. We combine conventional oral epithelial dysplasia grading with DNA ploidy analysis to examine the validity of this approach to risk assessment in a cohort of patients with known clinical outcomes.
METHODS: Sections from diagnostic biopsies were assessed for oral epithelial dysplasia using the WHO grading system, and DNA ploidy analysis was performed using established methods. Patients reviewed for a minimum of 5 years who did not develop oral squamous cell carcinoma were classified as "non-transforming" cases. Patients that developed oral squamous cell carcinoma ≥ 6 months after the initial diagnostic biopsy were classified as having "malignant transformation."
RESULTS: Ninety cases were included in the study. Seventy cases yielded informative DNA ploidy results. Of these 70 cases, 31 progressed to cancer. Oral epithelial dysplasia grading and DNA ploidy status were both significantly associated with clinical outcome (P P = 0.005) compared to cases with mild dysplasia. Aneuploidy had a hazard ratio of 2.09 (CI: 1.01, 4.32; P = 0.046) compared to cases with a diploid/tetraploid status. Receiver operating characteristic analysis gave an area under the curve of 0.617 for DNA ploidy status and 0.688 when DNA ploidy status was combined with dysplasia grading.
CONCLUSION: Our findings suggest that combining dysplasia grading with DNA ploidy status has clinical utility which could be used to develop novel management algorithms.
Gene expression changes associated with malignant transformation of oral potentially malignant disorders

Sathasivam HP, Casement J, Bates T, Sloan P, Thomson P, Robinson M, et al.

J Oral Pathol Med, 2021 Jan;50(1):60-67.
PMID: 32740996 DOI: 10.1111/jop.13090

BACKGROUND: A large number of oral squamous cell carcinomas (OSCCs) are believed to be preceded by oral potentially malignant disorders (OPMD) that have an increased likelihood of malignant transformation compared to clinically normal mucosa. This study was performed to identify differentially expressed genes between OPMDs that underwent malignant transformation (MT) and those that did not, termed "non-transforming" (NT) cases.
METHODS: Total RNA was extracted from formalin-fixed paraffin-embedded tissue biopsies of 20 OPMD cases with known clinical outcomes (10 MT vs. 10 NT). Samples were assessed for quantity, quality and integrity of RNA prior to sequencing. Analysis for differential gene expression between MT and NT was performed using statistical packages in R. Genes were considered to be significantly differentially expressed if the False Discovery Rate corrected P-value was 1.90). Analysis of RNA-Sequencing outputs revealed 41 genes (34 protein-coding; 7 non-coding) that were significantly differentially expressed between MT and NT cases. The log2 fold change for the statistically significant differentially expressed genes ranged from -2.63 to 2.48, with 23 protein-coding genes being downregulated and 11 protein-coding genes being upregulated in MT cases compared to NT cases.
CONCLUSION: Several candidate genes that may play a role in malignant transformation of OPMD have been identified. Experiments to validate these candidates are underway. It is anticipated that this work will contribute to better understanding of the etiopathogenesis of OPMD and development of novel biomarkers.
Fulltext Predicting the clinical outcome of oral potentially malignant disorders using transcriptomic-based molecular pathology

Sathasivam HP, Kist R, Sloan P, Thomson P, Nugent M, Alexander J, et al.

Br J Cancer, 2021 Aug;125(3):413-421.
PMID: 33972745 DOI: 10.1038/s41416-021-01411-z

BACKGROUND: This study was undertaken to develop and validate a gene expression signature that characterises oral potentially malignant disorders (OPMD) with a high risk of undergoing malignant transformation.
METHODS: Patients with oral epithelial dysplasia at one hospital were selected as the 'training set' (n = 56) whilst those at another hospital were selected for the 'test set' (n = 66). RNA was extracted from formalin-fixed paraffin-embedded (FFPE) diagnostic biopsies and analysed using the NanoString nCounter platform. A targeted panel of 42 genes selected on their association with oral carcinogenesis was used to develop a prognostic gene signature. Following data normalisation, uni- and multivariable analysis, as well as prognostic modelling, were employed to develop and validate the gene signature.
RESULTS: A prognostic classifier composed of 11 genes was developed using the training set. The multivariable prognostic model was used to predict patient risk scores in the test set. The prognostic gene signature was an independent predictor of malignant transformation when assessed in the test set, with the high-risk group showing worse prognosis [Hazard ratio = 12.65, p = 0.0003].
CONCLUSIONS: This study demonstrates proof of principle that RNA extracted from FFPE diagnostic biopsies of OPMD, when analysed on the NanoString nCounter platform, can be used to generate a molecular classifier that stratifies the risk of malignant transformation with promising clinical utility.
Clinicopathological features of squamous cell carcinoma of the oral cavity and oropharynx in young patients

Martinez RC, Sathasivam HP, Cosway B, Paleri V, Fellows S, Adams J, et al.

Br J Oral Maxillofac Surg, 2018 May;56(4):332-337.
PMID: 29628167 DOI: 10.1016/j.bjoms.2018.03.011

Our aim was to examine the clinicopathological features of squamous cell carcinoma (SCC) of the oral cavity and oropharynx in a group of young patients who were dignosed during a 15-year period (2000-2014). Patients' clinical details, risk factors, and survival were obtained from medical records. Formalin-fixed, paraffin-embedded, tissue was tested for high-risk human papillomavirus (HPV). The results were compared with those of a matching group of older patients. We identified 91 patients who were younger than 45 years old, and the 50 youngest patients were studied in detail. The male:female ratio was 2:1, with more tumours located in the oral cavity than in the oropharynx (35 compared with 15). HPV-related SCC was restricted to the oropharynx. When matched for site, stage and HPV status, five-year overall survival was similar in young and matched older patients (log-rank test, p=0.515). Our findings suggest that young patients with oral SCC have a disease profile similar to that of older patients with the condition. It is plausible that prognostic information generally available for oral cancers is applicable to young patients with the disease.
Data Set for the Reporting of Oral Cavity Carcinomas: Explanations and Recommendations of the Guidelines From the International Collaboration of Cancer Reporting

Müller S, Boy SC, Day TA, Magliocca KR, Richardson MS, Sloan P, et al.

Arch Pathol Lab Med, 2019 04;143(4):439-446.
PMID: 30500296 DOI: 10.5858/arpa.2018-0411-SA

The International Collaboration on Cancer Reporting is a nonprofit organization whose goal is to develop evidence-based, internationally agreed-upon standardized data sets for each cancer site for use throughout the world. Providing global standardization of pathology tumor classification, staging, and other reporting elements will lead to the objective of improved patient management and enhanced epidemiologic research. Carcinomas of the oral cavity continue to represent a significant oncologic management burden, especially as changes in alcohol and tobacco use on a global scale contribute to tumor development. Separation of oral cavity carcinomas from oropharyngeal tumors is also important, as management and outcome are quite different when human papillomavirus association is taken into consideration. Topics such as tumor thickness versus depth of invasion, pattern of invasive front, extent and size of perineural invasion, and margin assessment all contribute to accurate classification and staging of tumors. This review focuses on the data set developed for Carcinomas of the Oral Cavity Histopathology Reporting Guide, with discussion of the key elements developed for inclusion.
Changes in Epidermal Growth Factor Receptor Gene Copy Number during Oral Carcinogenesis

Bates T, Kennedy M, Diajil A, Goodson M, Thomson P, Doran E, et al.

Cancer Epidemiol Biomarkers Prev, 2016 Jun;25(6):927-35.
PMID: 27197272 DOI: 10.1158/1055-9965.EPI-15-0949

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a global healthcare problem associated with poor clinical outcomes. Early detection is key to improving patient survival. OSCC may be preceded by clinically recognizable lesions, termed oral potentially malignant disorders (OPMD). As histologic assessment of OPMD does not accurately predict their clinical behavior, biomarkers are required to detect cases at risk of malignant transformation. Epidermal growth factor receptor gene copy number (EGFR GCN) is a validated biomarker in lung non-small cell carcinoma. We examined EGFR GCN in OPMD and OSCC to determine its potential as a biomarker in oral carcinogenesis.
METHODS: EGFR GCN was examined by in situ hybridization (ISH) in biopsies from 78 patients with OPMD and 92 patients with early-stage (stages I and II) OSCC. EGFR ISH signals were scored by two pathologists and a category assigned by consensus. The data were correlated with patient demographics and clinical outcomes.
RESULTS: OPMD with abnormal EGFR GCN were more likely to undergo malignant transformation than diploid cases. EGFR genomic gain was detected in a quarter of early-stage OSCC, but did not correlate with clinical outcomes.
CONCLUSION: These data suggest that abnormal EGFR GCN has clinical utility as a biomarker for the detection of OPMD destined to undergo malignant transformation. Prospective studies are required to verify this finding. It remains to be determined if EGFR GCN could be used to select patients for EGFR-targeted therapies.
IMPACT: Abnormal EGFR GCN is a potential biomarker for identifying OPMD that are at risk of malignant transformation. Cancer Epidemiol Biomarkers Prev; 25(6); 927-35. ©2016 AACR.