METHODS: Seventeen cases each of SSCC, OSCC, NOM, and NS were evaluated. Each section was immunohistochemically stained with a rabbit polyclonal TIG3 antibody. The entire procedure was blinded and evaluated by 5 observers. Statistical analysis was performed using the chi-square test.
RESULTS: There was a significant decrease in TIG3 protein expression in OSCC and SSCC compared with that in NOM and NS (P = 0.008). The progressive loss of expression was observed as the grade of both malignancies increased. However, there was no significant difference in the expression among the normal tissue groups and within SCC groups of similar grades.
CONCLUSION: The present study suggests that the loss of TIG3 is an important event in carcinogenesis. TIG3 acts as a regulator of keratinocyte proliferation and terminal differentiation. Therefore, TIG3 could be a potential biomarker to differentiate aggressive and non-aggressive neoplasms.
METHODS: A retrospective review of 590 PMD patients treated in Northern England by CO2 laser surgery between 1996 and 2014 was carried out. Lesions exhibiting lichenoid or proliferative verrucous features were identified from the patient database and their clinicopathological features and outcome post-treatment determined at the study census date of 31 December 2014.
RESULTS: One hundred and 98 patients were identified as follows: 118 OLL and 80 PVL, most frequently leukoplakia at ventrolateral tongue and floor of mouth sites, equally distributed between males and females. Most exhibited dysplasia on incision biopsy (72% OLL; 85% PVL) and were treated by laser excision rather than ablation (88.1% OLL; 86.25% PVL). OLL were more common in younger patients (OLL 57.1 year; PVL 62.25 years; P = .008) and more likely than PVL to present as erythroleukoplakia (OLL 15.3%; PVL 2.5%; P = .003). Whilst no significant difference was seen between OLL and PVL achieving disease-free status (69.5% and 65%, respectively; P = .55), this was less than the overall PMD cohort (74.2%). MT was identified in 2 OLL (1.7%) and 2 PVL (2.5%) during follow-up.
CONCLUSION: One-third of PMD cases showed features of OLL or PVL, probably representing a disease presentation continuum. Post-treatment disease-free status was less common in OLL and PVL, although MT was infrequent.
METHODS: Detailed, retrospective clinico-pathological analysis of potentially malignant lesions undergoing malignant transformation, from a 590 patient cohort treated by interventional laser surgery and followed for a mean of 7.3 years, was undertaken. Clinical outcome was documented at study census date (31 December 2014).
RESULTS: A total of 99 patients (16.8%) developed cancer: 71 (12%) seen "unexpectedly" upon excision and 28 (4.8%) progressing to malignancy at a median of 87.3 months post-surgery. Thirty "unexpected" excisions were micro-invasive (42.3%) arising primarily in severely dysplastic precursors (75%) at ventro-lateral tongue and floor of mouth sites (54.5%); 1 patient (1.4%) had a cancer-related death, whilst 58 (81.7%) were disease free. A total of 19 of 28 "progressive" cancers (67.9%) arose at new sites, with erythroleukoplakia a significant predictor of malignancy (P = .0019). Nine (32.1%) developed at the same precursor site, with 6 (77.7%) on the ventro-lateral tongue and floor of mouth. Three (10.7%) were micro-invasive, 9 patients (32.1%) died from metastatic disease and 12 (42.9%) were disease free (P < .001).
CONCLUSION: Squamous carcinoma may arise at the site of a precursor lesion as transformation or new-site development via field cancerisation. Whilst interventional surgery facilitates early diagnosis and treatment of occult disease, thus reducing risk from same-site transformation, new-site cancer is a significant long-term risk for patients with potentially malignant disorder.
METHODS: A detailed, retrospective clinico-pathological review of treatment resistant potentially malignant lesions, from a 590 patient cohort treated by CO2 laser surgery and followed for a mean of 7.3 years, was undertaken. Clinical outcome was determined at study census date (31 December 2014).
RESULTS: A total of 87 patients (15%) exhibited PMD disease resistant to treatment: 34 (6%) became disease free following further treatment, whilst 53 (9%) had persistent disease despite intervention. Disease-free patients were younger, changed lesion appearance from erythroleukoplakia to leukoplakia (P = .004), developed further lesions at new sites, demonstrated reduction in dysplasia severity with time and required multiple treatments to achieve disease-free status (P = .0005). In contrast, persistent disease patients were older, male, often presented with proliferative verrucous leukoplakia (PVL) on gingival and alveolar sites, displayed less severe dysplasia initially and underwent laser ablation rather than excision (P = .027).
CONCLUSION: Despite clinico-pathological profiling of treatment resistant patients, the precise inter-relationship between the inherent nature of potentially malignant disease and the external influence of treatment intervention remains obscure.
MATERIALS AND RESULTS: Thirty-five paraffin-embedded ameloblastoma cases, ameloblastoma-derived cell lines (AM-1), and primary cultures of ameloblastoma stromal fibroblasts (ASF) were used. Immunohistochemistry, MTT assay, Western blotting, and RT-PCR were performed on these samples. Parenchyma-stromal CCN2 overexpression correlated significantly with fibrous-type stroma, but not with myxoid-type stroma, suggesting a role of CCN2 in fibrosis (P < 0.05). Recombinant CCN2 induction of enhanced ASF proliferation in AM-1 medium supports this view. Conversely, BMP4 and TGF-β were expressed in myxoid-type fibroblasts, but little expression was found in parenchyma. RANKL-positive and CD68-positive stromal cell populations were significantly greater in myxoid-type tumor areas than in fibrous-type tumor areas, while a higher Ki-67 labeling index was recorded in ameloblastoma with fibrous-type stroma. These data suggest that stromal properties influence bone resorption-related activities and growth rates, respectively.
CONCLUSIONS: These results suggest that the effects of secreted growth factors are governed by ameloblastoma parenchyma-stromal interactions. CCN2 promotes fibrogenesis independent of TGF-β signaling. Absence of CCN2 expression is associated with a phenotypic switch to a myxoid-type microenvironment that is conducive for TGF-β/BMP4 signaling to promote osteoclastogenesis.
MATERIALS AND METHOD: Eighty-seven paraffin-embedded ameloblastoma cases (20 unicystic, 47 solid/multicystic, 3 desmoplastic and 17 recurrent) were subjected to immunohistochemistry for expression of cortactin, N-WASP, WIP, Src kinase and F-actin, and findings correlated with clinicopathological parameters.
RESULTS: Invadopodia proteins (except Src kinase) and F-actin were widely detected in ameloblastoma (cortactin: n = 73/87, 83.9%; N-WASP: n = 59/87; 67.8%; WIP: n = 77/87; 88.5%; and F-actin: n = 87/87, 100%). Protein localization was mainly cytoplasmic and/or membranous, and occasionally nuclear for F-actin. Cortactin, which functions as an actin-scaffolding protein, demonstrated significantly higher expression levels within ameloblastoma tumoral epithelium than in stroma (P < 0.05). N-WASP, which coordinates actin polymerization and invadopodia-mediated extracellular matrix degradation, was overexpressed in the solid/multicystic subtype (P < 0.05). WIP, an upstream regulator of N-WASP, and F-actin were significantly upregulated along the tumour invasive front compared to tumour centres (P < 0.05). Except for males with cortactin overexpression, other clinical parameters (age, ethnicity and anatomical site) showed no significant correlations.
CONCLUSIONS: Present results suggest that local invasiveness of ameloblastoma is dependent upon the migratory potential of its tumour cells as defined by their distribution of cortactin, N-WASP and WIP in correlation with F-actin cytoskeletal dynamics.
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
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.
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).