Displaying all 15 publications

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  1. Siar CH, Mah MC, Gill PP
    Asian Pac J Cancer Prev, 2011;12(3):631-5.
    PMID: 21627356
    BACKGROUND: It is known that abnormal changes may occur in any part of the oral mucous membrane exposed to a carcinogen. Therefore patients with oral potentially malignant disorders (PMDs) are at risk of developing similar lesions at multiple sites.

    OBJECTIVES: To determine the risk of the contralateral mucosa in patients presenting with oral PMDs.

    MATERIALS AND METHODS: Sixty individuals with PMDs were selected for this study. These comprised 32 (53.3%) Indians, 23 (38.3%) Chinese, four (6.7%) Malays and one (1.7%) Nepalese. All selected cases had histopathological confirmation of their primary existing lesion as inclusion criteria. Cases that subsequently presented with a lesion in the corresponding anatomical site also underwent scalpel incisional biopsy on this second lesion to verify its diagnosis. The remaining cases that presented with unilateral PMDs at the time of study were subjected to a cytobrush biopsy on the normal looking contralateral mucosa.

    RESULTS: A total of 70 primary PMDs were detected in 60 patients. The most common PMD found was oral lichen planus (n=40, 57.1%). Of the 60 patients studied, 28 (46.6%) exhibited bilateral lesions either synchronously (n=21, 35.0%) or metachronously (n=7, 11.6%). The remaining cases that had undergone cytobrush biopsy on the corresponding anatomical site yielded normal cytological results.

    CONCLUSIONS: Present findings demonstrated that patients presenting with PMDs in the upper aerodigestive tract are at a greater risk of developing a second lesion most probably in the contralateral anatomical site.

    Matched MeSH terms: Precancerous Conditions/pathology*
  2. Prime SS, Cirillo N, Cheong SC, Prime MS, Parkinson EK
    Cancer Lett, 2021 10 10;518:102-114.
    PMID: 34139286 DOI: 10.1016/j.canlet.2021.05.025
    This study reviews the molecular landscape of oral potentially malignant disorders (OPMD). We examine the impact of tumour heterogeneity, the spectrum of driver mutations (TP53, CDKN2A, TERT, NOTCH1, AJUBA, PIK3CA, CASP8) and gene transcription on tumour progression. We comment on how some of these mutations impact cellular senescence, field cancerization and cancer stem cells. We propose that OPMD can be monitored more closely and more dynamically through the use of liquid biopsies using an appropriate biomarker of transformation. We describe new gene interactions through the use of a systems biology approach and we highlight some of the first studies to identify functional genes using CRISPR-Cas9 technology. We believe that this information has translational implications for the use of re-purposed existing drugs and/or new drug development. Further, we argue that the use of digital technology encompassing clinical and laboratory-based data will create relevant datasets for machine learning/artificial intelligence. We believe that therapeutic intervention at an early molecular premalignant stage should be an important preventative strategy to inhibit the development of oral squamous cell carcinoma and that this approach is applicable to other aerodigestive tract cancers.
    Matched MeSH terms: Precancerous Conditions/pathology
  3. Goodson ML, Smith DR, Thomson PJ
    J Oral Pathol Med, 2017 Nov;46(10):896-901.
    PMID: 28833675 DOI: 10.1111/jop.12627
    BACKGROUND: Oral potentially malignant disorders (PMD) harbour unpredictable risk for squamous cell carcinoma development. Current management requires tissue biopsy for histopathology characterisation, dysplasia grading and targeted intervention to "high-risk" lesions, although evidence-based guidelines are limited and diagnoses subjective. This study investigated the use of adjunctive oral brush biopsy techniques during the management of PMD in a UK hospital population.

    METHODS: Retrospective review of a 310 PMD patient cohort presenting to Maxillofacial Surgery in Newcastle upon Tyne with new, single-site lesions between December 2009 and May 2014. Patients underwent Orcellex® brush biopsy and liquid-based cytology examination in addition to conventional biopsy techniques, with management proceeding along established care pathways. Patient demographics, cytology data, most significant histopathology diagnoses and clinical outcome were all documented at the study census date (31.12.15).

    RESULTS: A total of 170 male & 140 female patients (age range 18-91 years), exhibiting primarily leukoplakia (86.5%) at floor of mouth and ventrolateral tongue sites (44.9%), were identified. Management comprised: observation (49.7%), laser surgery (44.9%), antifungal treatment (3.5%) and Head & Neck clinic referral following cancer diagnosis (1.9%). Clinical outcomes were as follows: disease free (51.3%), persistent PMD (42.3%) and malignant transformation (6.4%). Histology and cytology diagnoses strongly correlated (r = .305). Treatment modality, lesion site, histology and cytology diagnoses were the best predictors of clinical outcome.

    CONCLUSIONS: Orcellex® brush cytology provides reliable diagnoses consistent with conventional histopathology and offers less invasive, adjunctive assessment appropriate for long-term monitoring of patients in specialist clinics.

    Matched MeSH terms: Precancerous Conditions/pathology*
  4. Thomson PJ, Goodson ML, Smith DR
    J Oral Pathol Med, 2017 Nov;46(10):902-910.
    PMID: 28891106 DOI: 10.1111/jop.12641
    BACKGROUND: Contemporary potentially malignant disorder management is based upon provisional histological diagnosis followed by interventional surgery to excise or ablate 'high-risk' mucosal lesions. Although the majority of patients achieve disease-free status post-treatment, others develop further or persistent disease unresponsive to intervention.

    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.

    Matched MeSH terms: Precancerous Conditions/pathology*
  5. Norfadzilah MY, Pailoor J, Retneswari M, Chinna K, Noor LM
    Malays J Pathol, 2011 Dec;33(2):89-94.
    PMID: 22299208 MyJurnal
    Patients with pancreatic adenocarcinoma are known to have a high mortality rate. The 5-year survival rate still remains low even now compared to that of the 1960's despite new advances in management including surgery, chemotherapy, pathological classification and molecular diagnostic technologies. Precursors to invasive pancreatic adenocarcinoma have been identified in the last ten years that include mucinous cystic neoplasm, intraductal papillary mucinous neoplasm and pancreatic intraepithelial neoplasia. p53 protein accumulation in the nuclei is a common molecular event in most human neoplasms. Our objective is to investigate p53 expression in pancreatic adenocarcinoma and precursor lesions and their significance. The selected study material encompassed 31 invasive ductal adenocarcinoma, 15 mucinous cystic neoplasm and papillary mucinous neoplasm, and 27 cases of pancreatic intraepithelial neoplasia including grade 1, 2 and 3. Immunoscore was given for each case based on intensity of staining and percentage of cells positive and compared between precursor lesions and invasive adenocarcinoma. A score of 50 and above was considered significant. The results showed that p53 expression increased progressively and significantly with the grade of pancreatic intraepithelial neoplasia and adenocarcinoma (p-value < 0.001). These findings support the concept of multistep carcinogenesis in pancreatic adenocarcinoma and suggest that p53 inactivation occurs in the progression of precursors to pancreatic adenocarcinoma.
    Matched MeSH terms: Precancerous Conditions/pathology
  6. Lim JS, Tang SP, Siar CH
    Asian Pac J Cancer Prev, 2009;10(6):1071-4.
    PMID: 20192586
    BACKGROUND: Conventional methods for writing case notes detailing the progress of oral lichen planus (OLP), a precancerous condition that requires long-term surveillance, is both time-consuming and tedious for the busy clinician.

    OBJECTIVES: To design and perform a simple surveillance on OLP patients based on colour-coded topography mouth maps (TMM).

    MATERIALS AND METHODS: Three colour-coded TMM were employed: red for OLP in high risk oral mucosal sites, yellow for cases showing improvement and green for asymptomatic lesions at each recall visit. In this preliminary study, these were applied on 30 histologically confirmed OLP individuals attending the Oral Medicine Clinic at the Department of Oral Pathology, Oral Medicine and Periodontology, Faculty of Dentistry, University of Malaya. The sites and extent of OLP lesions were charted on either red, yellow or green TMM based on defined criteria. This surveillance evaluated OLP in relation to patientandapos;s age, race, gender, underlying systemic conditions, oral habits, initial onset of OLP, oral manifestations and presence/absence of clinically suspicious areas.

    RESULTS: Study sample comprised 4 (13.3%) Malays, 9 (30.0%) Chinese and 17 (56.7%) Indians. Most OLP patients belong to the green TMM (n= 14, 46.6%) group followed by red (n= 11, 36.7%) and yellow (n= 5, 16.7%) groups. Of the 11 cases with red TMM, rebiopsy was performed on 4 cases but no dysplasia was detected. Any local confounding factors namely periodontal disease or faulty dental restorations were managed accordingly.

    CONCLUSIONS: TMM is simple to use and aided the clinicians in terms of time saving and patient management. Hence, follow-up of OLP patients can be carried out more efficiently and appropriately. TMM can be used for surveillance of other oral precancerous lesions and conditions.

    Matched MeSH terms: Precancerous Conditions/pathology*
  7. Kumar SK, Zain RB, Ismail SM, Cheong SC
    J Exp Clin Cancer Res, 2005 Dec;24(4):639-46.
    PMID: 16471328
    Human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, is strongly associated with telomerase activity implicated in cellular immortalization and tumorigenesis. In situ detection of hTERT will aid in determining the localization of telomerase positive cells. The aim of this study was to detect hTERT protein expression in multistep oral carcinogenesis using paraffin embedded tissue samples, and to study the relationship of hTERT expression with different histological stages in oral carcinogenesis. Normal (n = 4), hyperplastic (n = 4), dysplastic (n = 4) and neoplastic (n = 10) oral epithelia representing different histological stages in oral carcinogenesis were included in the study. hTERT protein detection was done by immunohistochemistry (IHC) technique. Nuclear staining intensities were noted and the hTERT-labelling index was determined. Dysplastic and neoplastic oral epithelia showed an increased percentage of hTERT positive cells (Grade 4: > 50% positive staining nuclei) with intense staining in the basal, parabasal and superficial layers of the epithelia, unlike normal oral mucosa which showed intense staining only in the basal and parabasal cell layers, which are the normal proliferative progenitor compartments. hTERT protein expression was elevated with the corresponding advancement of the histological stages of oral carcinogenesis, from normal to hyperplasia to dysplasia to carcinoma. There seems to be an upregulation of hTERT protein expression during the progression of oral cancer, therefore, this may indicate the feasibility of IHC detection of hTERT protein in oral carcinogenesis as a potential diagnostic or prognostic marker.
    Matched MeSH terms: Precancerous Conditions/pathology
  8. Zain RB, Sakamoto F, Shrestha P, Mori M
    Malays J Pathol, 1995 Jun;17(1):23-30.
    PMID: 8907001
    Proliferating cell nuclear antigen (PCNA) is a well known marker for cell proliferation. It tends to accumulate in the late G1 and S-phase of the cell cycle. A monoclonal antibody (MoAb) against PCNA is now available and it can react with paraffin-embedded specimens. In the present study, PCNA immunohistochemical staining of 36 cases of oral cancer specimens obtained from surgery were investigated. The results showed differing nuclear staining patterns for PCNA in normal, hyperplastic and dysplastic epithelium, early cancer and 3 levels of differentiation for squamous cell carcinoma of the oral cavity. It appears that PCNA can be a useful marker in delineating normal epithelium and hyperplastic epithelium from dysplasia in the oral cavity. The use of PCNA staining may further emphasize the conventional histopathological grading of well-differentiated, moderately-differentiated and poorly-differentiated oral squamous cell carcinoma but is still dependent on basic criteria as observed without immunostaining. PCNA expression for all grades of squamous cell carcinoma are present at the deep, infiltrative margins.
    Matched MeSH terms: Precancerous Conditions/pathology
  9. Htwe TT
    Singapore Med J, 2012 Mar;53(3):159-63.
    PMID: 22434287
    Endemic goitre is a major concern in many parts of the world, including Southeast Asia. Goitrous thyroid lesion is postulated as a precursor lesion to thyroid cancer (TC). This paper reviews the prevalence rates and characteristics of TC among cases of goitrous thyroid-swelling in different parts of Malaysia and Myanmar. Recorded data from hospital-based retrospective studies of thyroid cases, whose study periods ranged from three to 11 years, were analysed. These included research findings from the author's publications as well as other published review articles of retrospective analyses. The incidence of TC varies among gender, age, race/ethnicity and histological type. There appears to be a higher rate of occurrence among females aged 21-60 years. Papillary thyroid carcinoma is the more common histological type compared to follicular cancer. This review also presents a descriptive analysis and discussion on studies conducted in other countries. Further exploration is warranted in order to uncover the possible risk factors for the rising incidence of TC.
    Matched MeSH terms: Precancerous Conditions/pathology*
  10. Ram S, Siar CH
    Int J Oral Maxillofac Surg, 2005 Jul;34(5):521-7.
    PMID: 16053872
    Chemiluminescence was evaluated as a diagnostic aid in the detection of oral cancer and potentially malignant epithelial lesions (PMELs) by comparing it against 1% tolonium chloride mouth rinse. Forty-six clinically identified lesions [14 primary squamous cell carcinoma (SCC), 26 PMELs and 6 benign lesions] and five cases of normal oral mucosa from 40 subjects (inclusive of 10 previously treated SCC cases) were examined with a commercial chemiluminescent kit (Vizilite) and tolonium chloride. Biopsy and histological verification of 31 lesions disclosed 14 SCC (45.2%), 10 epithelial dysplasias (32.3%), 5 lichen planus (16.1%) and 2 benign lesions (6.4%). For the remaining 15 lesions, a biopsy was not performed owing to patient's lack of consent or ill-health. The five cases of normal oral mucosa which tested negative for both tools were also not biopsied for ethical reasons. Sensitivity for Vizilite and tolonium chloride was 100% and 70.3%, respectively; and specificity was 14.2% for Vizilite and 25% for tolonium chloride. Their accuracy was 80.6% and 64.5%, respectively. Current findings suggest that chemiluminescence is a more reliable diagnostic tool than tolonium chloride in the detection of oral cancer and PMELs, and for follow-up of patients treated for the same.
    Matched MeSH terms: Precancerous Conditions/pathology
  11. Visvanathan R, Thambidorai CR, Myint H
    Ann Acad Med Singap, 1992 Nov;21(6):830-2.
    PMID: 1338270
    Two patients, members of one family, with Peutz-Jeghers syndrome are described who underwent surgery for bowel obstruction. Both had multiple polyps in the gastrointestinal tract. Severe dysplasia and adenomatous change were present in two hamartomatous polyps adjacent to a stenosing colonic carcinoma in one patient and moderate dysplasia and adenomatous change were observed in two hamartomatous rectal polyps in his son. These changes support recent reports in the literature of progression towards neoplasia in these lesions.
    Matched MeSH terms: Precancerous Conditions/pathology*
  12. Thomas G, Tr S, George S P, Somanathan T, Sarojam S, Krishnankutti N, et al.
    Asian Pac J Cancer Prev, 2020 Feb 01;21(2):309-316.
    PMID: 32102504 DOI: 10.31557/APJCP.2020.21.2.309
    BACKGROUND: Although leukoplakia shows a higher risk for malignant transformation to oral cancer, currently there are no clinically relevant biomarker which can predict the potentially high risk leukoplakia. This study aimed to investigate the genetic alterations such as DNA ploidy, telomerase expression and DNA repair capacity as predictive markers of malignant transformation risk of leukoplakia.

    METHODS: The study was initiated in September 2005 and patients were followed up to March 2014. Two hundred patients with oral leukoplakia, 100 patients with oral cancer and 100 healthy, age and sex matched adults with normal oral mucosa as controls were recruited. The DNA ploidy content was measured by high resolution flow cytometry, level of telomerase expression was identified by TRAP assay and intrinsic DNA repair capacity was measured by mutagen induced chromosome sensitivity assay of cultured peripheral blood lymphocytes. The Chi-square test or Fisher's Exact test was used for comparison of categorical variables between biomarkers. A p value less than or equal to 0.05 was considered as statistically significant. Analysis was performed with SPSS software version 16. Logistic regression was used to find the association between the dependent and three independent variables.

    RESULTS: There was significant difference in the distribution of ploidy status, telomerase activity and DNA repair capacity among control, leukoplakia and oral cancer group (p<0.001). When the molecular markers were compared with histological grading of leukoplakia, both DNA ploidy analysis and telomerase activity showed statistical significance (p<0.001). Both aneuploidy and telomerase positivity was found to coincide with high-risk sites of leukoplakia and were statistically significant (p.

    Matched MeSH terms: Precancerous Conditions/pathology
  13. Siar CH, Oo VP, Nagatsuka H, Nakano K, Ng KH, Kawakami T
    Eur J Med Res, 2009 Jul 22;14(7):315-9.
    PMID: 19661015
    STATEMENT OF THE PROBLEM: Dysplasia, the morphological yardstick of epithelial precursor lesions, is the collective term for a variety of architectural and cytological changes within the altered oral epithelium. Angiogenic squamous dysplasia (ASD), a distinct morphological characteristic in pre-invasive bronchial lesions, describes the presence of capillary tufts that are closely juxtaposed to and projecting into the dysplastic bronchial epithelium.

    OBJECTIVE: To determine whether ASD-like phenomenon occurs in oral epithelial precursor lesions, and to speculate on its relevance.

    METHODS: Twenty cases each of mild, moderate and severe oral dysplasia (inclusive of carcinoma-in-situ), and 10 normal oral mucosa (normal controls) were serial sectioned for H and E staining, and for microvessel density (MVD) scoring with CD31, CD34 and CD105. Microcapillary pattern images were digitally captured for 3-D reconstruction.

    RESULTS: Oral ASD foci consisting of CD31- and CD34-positive capillary loops abutting onto the overlying dysplastic oral epithelium (and causing it to assume an irregular or papillary surface configuration) were identified in moderate (3/20; 15%) and severe dysplasia (13/20; 65%), but not in normal oral mucosa and mild dysplasia. MVD score demonstrated increasing vascularity as epithelium progressed from normal to severe dysplasia (p<0.05). CD105 demonstrated increase neovascularization in all dysplasia grades (p<0.05).

    CONCLUSIONS: These preliminary findings taken together suggest that: 1. ASD-like phenomenon may be an important intermediary biomarker in oral precursor lesions; and 2. architectural alterations of the entire disturbed mucosa may be a more useful pre-malignancy index.

    Matched MeSH terms: Precancerous Conditions/pathology
  14. Kumarasamy V, Kuppusamy UR, Jayalakshmi P, Samudi C, Ragavan ND, Kumar S
    PLoS One, 2017;12(8):e0183097.
    PMID: 28859095 DOI: 10.1371/journal.pone.0183097
    Colorectal cancer (CRC) is one the most commonly diagnosed cancers worldwide and the number is increasing every year. Despite advances in screening programs, CRC remains as the second leading cause of cancer deaths in the United States. Oxidative stress plays an important role in the molecular mechanisms of colorectal cancer (CRC) and has been shown to be associated with Blastocystis sp., a common intestinal microorganism. In the present study, we aimed to identify a role for Blastocystis sp. in exacerbating carcinogenesis using in vivo rat model. Methylene blue staining was used to identify colonic aberrant crypt foci (ACF) and adenomas formation in infected rats whilst elevation of oxidative stress biomarker levels in the urine and serum samples were evaluated using biochemical assays. Histological changes of the intestinal mucosa were observed and a significant number of ACF was found in Blastocystis sp. infected AOM-rats compared to the AOM-controls. High levels of urinary oxidative indices including advanced oxidative protein products (AOPP) and hydrogen peroxide were observed in Blastocystis sp. infected AOM-rats compared to the uninfected AOM-rats. Our study provides evidence that Blastocystis sp. has a significant role in enhancing AOM-induced carcinogenesis by resulting damage to the intestinal epithelium and promoting oxidative damage in Blastocystis sp. infected rats.
    Matched MeSH terms: Precancerous Conditions/pathology
  15. Zain RB, Ikeda N, Gupta PC, Warnakulasuriya S, van Wyk CW, Shrestha P, et al.
    J Oral Pathol Med, 1999 Jan;28(1):1-4.
    PMID: 9890449
    A variety of betel/areca nut/tobacco habits have been reviewed and categorized because of their possible causal association with oral cancer and various oral precancerous lesions and conditions, and on account of their widespread occurrence in different parts of the world. At a recent workshop in Kuala Lumpur it was recommended that "quid" be defined as "a substance, or mixture of substances, placed in the mouth or chewed and remaining in contact with the mucosa, usually containing one or both of the two basic ingredients, tobacco and/or areca nut, in raw or any manufactured or processed form." Clear delineations on contents of the quid (areca nut quid, tobacco quid, and tobacco and areca nut quid) are recommended as absolute criteria with finer subdivisions to be added if necessary. The betel quid refers to any quid wrapped in betel leaf and is therefore a specific variety of quid. The workshop proposed that quid-related lesions should be categorized conceptually into two categories: first, those that are diffusely outlined and second, those localized at the site where a quid is regularly placed. Additional or expanded criteria and guidelines were proposed to define, describe or identify lesions such as chewer's mucosa, areca nut chewer's lesion, oral submucous fibrosis and other quid-related lesions. A new clinical entity, betel-quid lichenoid lesion, was also proposed to describe an oral lichen planus-like lesion associated with the betel quid habit.
    Matched MeSH terms: Precancerous Conditions/pathology
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