Displaying publications 21 - 40 of 82 in total

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  1. Lee KW, Chin CT
    Br. J. Cancer, 1970 Sep;24(3):433-41.
    PMID: 5475751
    Sixty-two "leukoplakias" from the cheeks of betel-nut chewers in West Malaysia were studied histologically. Ten biopsies were from non-tobacco betel-nut chewers. An amorphous von Kossa positive layer was seen on the keratin surface in 42 specimens. Tobacco did not appear essential for its formation, and it appeared to be significantly associated with parakeratosis. Its possible significance as a cuticle-like layer prolonging contact between carcinogens and the mucosa is discussed.Parakeratosis appeared to be the most common form of cornification seen, and the mitotic activity in parakeratinized leukoplakias appeared to be significantly greater than orthokeratinized leukoplakias.Comparison with studies on other population samples using different quids suggested that severe histological changes were more likely to be seen when tobacoo-containing quids were chewed as compared to non-tobacco-containing quids.An attempt to correlate the histological changes seen with the clinical habit in leukoplakias from chewers using tobacco-containing quids suggested that epithelial atrophy appeared to be significantly related to the duration of the habit but not to the "intensity" of the habit.
    Matched MeSH terms: Mouth Neoplasms/pathology*
  2. Ghani WMN, Ramanathan A, Prime SS, Yang YH, Razak IA, Abdul Rahman ZA, et al.
    Cancer Invest, 2019;37(7):275-287.
    PMID: 31307249 DOI: 10.1080/07357907.2019.1635614
    Previous studies found that ethnicity influences oral cancer patients' survival; however, most studies were limited to certain ethnic groups particularly from the West, thus of limited relevance to Asians where the disease is most prevalent. We investigated the relationship between ethnicity and patient survival in multi-racial Malaysia. 5-year survival rate was 40.9%. No statistically significant difference was observed in survival between Malays, Chinese, Indians and Indigenous peoples (45.7%, 44.0%, 41.3%, 27.7% respectively). Increased tumor size, lymph node involvement and advanced tumor were predictive of poor survival. We conclude that ethnicity has no effect on survival or its prognostic indicators.
    Matched MeSH terms: Mouth Neoplasms/pathology
  3. Vincent-Chong VK, Salahshourifar I, Woo KM, Anwar A, Razali R, Gudimella R, et al.
    PLoS One, 2017;12(4):e0174865.
    PMID: 28384287 DOI: 10.1371/journal.pone.0174865
    BACKGROUND: Cancers of the oral cavity are primarily oral squamous cell carcinomas (OSCCs). Many of the OSCCs present at late stages with an exceptionally poor prognosis. A probable limitation in management of patients with OSCC lies in the insufficient knowledge pertaining to the linkage between copy number alterations in OSCC and oral tumourigenesis thereby resulting in an inability to deliver targeted therapy.

    OBJECTIVES: The current study aimed to identify copy number alterations (CNAs) in OSCC using array comparative genomic hybridization (array CGH) and to correlate the CNAs with clinico-pathologic parameters and clinical outcomes.

    MATERIALS AND METHODS: Using array CGH, genome-wide profiling was performed on 75 OSCCs. Selected genes that were harboured in the frequently amplified and deleted regions were validated using quantitative polymerase chain reaction (qPCR). Thereafter, pathway and network functional analysis were carried out using Ingenuity Pathway Analysis (IPA) software.

    RESULTS: Multiple chromosomal regions including 3q, 5p, 7p, 8q, 9p, 10p, 11q were frequently amplified, while 3p and 8p chromosomal regions were frequently deleted. These findings were in confirmation with our previous study using ultra-dense array CGH. In addition, amplification of 8q, 11q, 7p and 9p and deletion of 8p chromosomal regions showed a significant correlation with clinico-pathologic parameters such as the size of the tumour, metastatic lymph nodes and pathological staging. Co-amplification of 7p, 8q, 9p and 11q regions that harbored amplified genes namely CCND1, EGFR, TPM2 and LRP12 respectively, when combined, continues to be an independent prognostic factor in OSCC.

    CONCLUSION: Amplification of 3q, 5p, 7p, 8q, 9p, 10p, 11q and deletion of 3p and 8p chromosomal regions were recurrent among OSCC patients. Co-alteration of 7p, 8q, 9p and 11q was found to be associated with clinico-pathologic parameters and poor survival. These regions contain genes that play critical roles in tumourigenesis pathways.

    Matched MeSH terms: Mouth Neoplasms/pathology
  4. Ramanathan K
    Med J Malaysia, 1979 Sep;34(1):28-31.
    PMID: 542146
    Matched MeSH terms: Mouth Neoplasms/pathology
  5. Arzmi MH, Cirillo N, Lenzo JC, Catmull DV, O'Brien-Simpson N, Reynolds EC, et al.
    Carcinogenesis, 2019 03 12;40(1):184-193.
    PMID: 30428016 DOI: 10.1093/carcin/bgy137
    Microbial infection has been shown to involve in oral carcinogenesis; however, the underlying mechanisms remain poorly understood. The present study aimed to characterize the growth of oral microorganisms as both monospecies and polymicrobial biofilms and determine the effects of their products on oral keratinocytes. Candida albicans (ALC3), Actinomyces naeslundii (AN) and Streptococcus mutans (SM) biofilms or a combination of these (TRI) were grown in flow-cell system for 24 h. The biofilms were subjected to fluorescent in situ hybridization using species-specific probes and analysed using confocal laser scanning microscopy. The effluent derived from each biofilm was collected and incubated with malignant (H357) and normal (OKF6) oral keratinocytes to assess extracellular matrix adhesion, epithelial-mesenchymal transition (EMT) and cytokines expression. Incubation of OKF6 with ALC3 and TRI effluent significantly decreased adhesion of the oral keratinocyte to collagen I, whereas incubation of H357 with similar effluent increased adhesion of the oral keratinocyte to laminin I, significantly when compared with incubation with artificial saliva containing serum-free medium (NE; P < 0.05). In OKF6, changes in E-cadherin and vimentin expression were not consistent with EMT although there was evidence of a mesenchymal to epithelial transition in malignant oral keratinocytes incubated with AN and SM effluent. A significant increase of pro-inflammatory cytokines expression, particularly interleukin (IL)-6 and IL-8, was observed when H357 was incubated with all biofilm effluents after 2- and 24-h incubation when compared with NE (P < 0.05). In conclusion, C.albicans, A.naeslundii and S.mutans form polymicrobial biofilms which differentially modulate malignant phenotype of oral keratinocytes.
    Matched MeSH terms: Mouth Neoplasms/pathology*
  6. Pentenero M, Bowers L, Jayasinghe R, Cheong SC, Farah CS, Kerr AR, et al.
    Oral Dis, 2019 Jun;25 Suppl 1:79-87.
    PMID: 31140691 DOI: 10.1111/odi.13051
    Long non-coding RNAs (lncRNA) modulate gene expression at the epigenetic, transcriptional and post-transcriptional levels and are involved in tumorigenesis. They can form complex secondary and tertiary structures and have been shown to act as precursors, enhancers, reservoirs and decoys in the complex endogenous RNA network. They were first reported in relation to oral squamous cell carcinoma (OSCC) in 2013. Here, we summarise the functional roles and pathways of the most commonly studied lncRNAs in OSCC. Existing research demonstrates the involvement of lncRNA within pivotal pathways leading to the development and spread of OSCC, including interactions with key cancer-associated microRNAs such as miR-21. The number of studies on lncRNA and OSCC remains limited in this new field. As evidence grows, the tissue-specific expression patterns of lncRNAs should further advance our understanding of the altered regulatory networks in OSCC and possibly reveal new biomarkers and therapeutic targets.
    Matched MeSH terms: Mouth Neoplasms/pathology
  7. 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: Mouth Neoplasms/pathology
  8. Ahmad WMAW, Yaqoob MA, Noor NFM, Ghazali FMM, Rahman NA, Tang L, et al.
    Biomed Res Int, 2021;2021:5436894.
    PMID: 34904115 DOI: 10.1155/2021/5436894
    Background: Cancer is primarily caused by smoking, alcohol, betel quit, a series of genetic alterations, and epigenetic abnormalities in signaling pathways, which result in a variety of phenotypes that favor the development of OSCC. Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, accounting for 80-90% of all oral malignant neoplasms. Oral cancer is relatively common, and it is frequently curable when detected and treated early enough. The tumor-node-metastasis (TNM) staging system is used to determine patient prognosis; however, geographical inaccuracies frequently occur, affecting management.

    Objective: To determine the additional relationship between factors discovered by searching for sociodemographic and metastasis factors, as well as treatment outcomes, which could help improve the prediction of the survival rate in cancer patients. Material and Methods. A total of 56 patients were recruited from the ambulatory clinic at the Hospital Universiti Sains Malaysia (USM). In this retrospective study, advanced computational statistical modeling techniques were used to evaluate data descriptions of several variables such as treatment, age, and distant metastasis. The R-Studio software and syntax were used to implement and test the hazard ratio. The statistics for each sample were calculated using a combination model that included methods such as bootstrap and multiple linear regression (MLR).

    Results: The statistical strategy showed R demonstrates that regression modeling outperforms an R-squared. It demonstrated that when data is partitioned into a training and testing dataset, the hybrid model technique performs better at predicting the outcome. The variable validation was determined using the well-established bootstrap-integrated MLR technique. In this case, three variables are considered: age, treatment, and distant metastases. It is important to note that three things affect the hazard ratio: age (β 1: -0.006423; p < 2e - 16), treatment (β 2: -0.355389; p < 2e - 16), and distant metastasis (β 3: -0.355389; p < 2e - 16). There is a 0.003469102 MSE for the linear model in this scenario.

    Conclusion: In this study, a hybrid approach combining bootstrapping and multiple linear regression will be developed and extensively tested. The R syntax for this methodology was designed to ensure that the researcher completely understood the illustration. In this case, a hybrid model demonstrates how this critical conclusion enables us to better understand the utility and relative contribution of the hybrid method to the outcome. The statistical technique used in this study, R, demonstrates that regression modeling outperforms R-squared values of 0.9014 and 0.00882 for the predicted mean squared error, respectively. The conclusion of the study establishes the superiority of the hybrid model technique used in the study.

    Matched MeSH terms: Mouth Neoplasms/pathology
  9. Senarath NH, Jayasooriya PR, Siriwardena BSMS, Tilakaratne WM
    Asian Pac J Cancer Prev, 2021 Aug 01;22(8):2313-2321.
    PMID: 34452541 DOI: 10.31557/APJCP.2021.22.8.2313
    BACKGROUND: Epithelial dysplasia (ED) at oral cancer excision margins is a frequent finding. Dysplastic epithelium at excision margins may not be similar to dysplasia in Oral potentially malignant disorders (OPMD) as malignant transformation has already taken place. Therefore, management of ED at excision margins should be different to that of OPMD. ED creates a dilemma in relation to further management of cancer patients, since there are no accepted guidelines. Therefore, the objective of this review is to analyze  existing literature and to arrive at evidence based recommendations for the management of ED at excision margins.

    METHODS: A comprehensive string was run on PubMed, Medscape and Medline. The final outcome included 113 studies. Finally, the most relevant 10 articles were critically assessed for inclusion and exclusion criteria against various parameters.

    RESULTS AND CONCLUSIONS:   Severe and Moderate ED need re-excision in order to improve prognosis. There is not enough sound evidence for the management of Mild ED at excision margins of oral squamous cell carcinoma. Guidelines for the management of ED at excision margins should be formulated after comprehensive multi center studies using lager cohorts of patients.
    .

    Matched MeSH terms: Mouth Neoplasms/pathology*
  10. 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: Mouth Neoplasms/pathology*
  11. Thomson PJ, Goodson ML, Smith DR
    J Oral Pathol Med, 2017 Nov;46(10):888-895.
    PMID: 28833670 DOI: 10.1111/jop.12625
    BACKGROUND: Oral potentially malignant disorders harbour variable and unpredictable risk for squamous carcinoma development. Whilst current management strategies utilise histopathological diagnoses, dysplasia grading and targeted intervention for "high-risk" lesions, clinicians are unable to predict malignant potential.

    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.

    Matched MeSH terms: Mouth Neoplasms/pathology*
  12. 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: Mouth Neoplasms/pathology*
  13. Azhar N, Doss JG
    Asian Pac J Cancer Prev, 2018 Oct 26;19(10):2935-2941.
    PMID: 30362327
    Background: The aim of this study was to explore reasons for delayed health-seeking for late stage oral cancer patients. Methods: Semi-structured in-depth interviews were conducted with 35 oral cancer patients with TNM stage III to IV disease, who were treated at six tertiary regional centres managing oral cancer throughout Malaysia. Interviews were audio-recorded, transcribed verbatim, coded using NVivo (version 10.0) qualitative software and analysed using framework analysis. Results: Participants interpreted their early symptoms as a minor condition and did not consider it as requiring immediate attention. Four types of coping strategies causing delayed help-seeking emerged: 1) self-remedy 2) self-medication 3) seeking traditional healers and 4) consulting general medical practitioners (GPs) instead of dentists. Socio-economic factors, cultural beliefs and religious practices have some influence on diagnostic delay. Conclusion: Low levels of public knowledge and awareness regarding early signs and symptoms of oral cancer as well as GPs’ misdiagnosis of early lesions results in delayed diagnosis.
    Matched MeSH terms: Mouth Neoplasms/pathology*
  14. Pentenero M, Bowers LM, Jayasinghe R, Yap T, Cheong SC, Kerr AR, et al.
    Oral Dis, 2019 Jun;25 Suppl 1(Suppl 1):88-101.
    PMID: 31140697 DOI: 10.1111/odi.13076
    BACKGROUND: Long non-coding RNAs (lncRNAs) have important roles in regulating gene expression pertaining to cell proliferation, survival, migration and genomic stability. Dysregulated expression of lncRNAs is implicated in cancer initiation, progression and metastasis.

    OBJECTIVES: To explore, map and summarize the extent of evidence from clinical studies investigating the differential expression of lncRNAs in oral/tongue squamous cell carcinoma.

    METHODS: PubMed, Scopus and Web of Science were used as search engines. Clinical, full-length, English language studies were included. PRISMA-ScR protocol was used to evaluate and present results. The present scoping review summarizes relationships of the differential expression of lncRNAs with the presence of tumour and with clinicopathological features including survival.

    RESULTS: Almost half of the investigated transcripts have been explored in more than one study, yet not always with consistent results. The collected data were also compared to the limited studies investigating oral epithelial dysplasia. Data are not easily comparable, first because of different methods used to define what differential expression is, and second because only a limited number of studies performed multivariate analyses to identify clinicopathological features associated with the differentially expressed lncRNAs.

    CONCLUSIONS: Standard methods and more appropriate data analyses are needed in order to achieve reliable results from future studies.

    Matched MeSH terms: Mouth Neoplasms/pathology
  15. Khor GH, Froemming GR, Zain RB, Abraham MT, Thong KL
    Asian Pac J Cancer Prev, 2014;15(20):8957-61.
    PMID: 25374236
    BACKGROUND: Promoter hypermethylation leads to altered gene functions and may result in malignant cellular transformation. Thus, identification of biomarkers for hypermethylated genes could be useful for diagnosis, prognosis, and therapeutic treatment of oral squamous cell carcinoma (OSCC).

    OBJECTIVES: To screen hypermethylated genes with a microarray approach and to validate selected hypermethylated genes with the methylation-specific polymerase chain reaction (MSPCR).

    MATERIALS AND METHODS: Genome-wide analysis of normal oral mucosa and OSCC tissues was conducted using the Illumina methylation microarray. The specified differential genes were selected and hypermethylation status was further verified with an independent cohort sample of OSCC samples. Candidate genes were screened using microarray assay and run by MSPCR analysis.

    RESULTS: TP73, PIK3R5, and CELSR3 demonstrated high percentages of differential hypermethylation status.

    CONCLUSIONS: Our microarray screening and MSPCR approaches revealed that the signature candidates of differentially hypermethylated genes may possibly become potential biomarkers which would be useful for diagnostic, prognostic and therapeutic targets of OSCC in the near future.

    Matched MeSH terms: Mouth Neoplasms/pathology
  16. Poovaneswaran S, Paleri V, Charlton F, Dobrowsky W, Kelly C
    Med J Malaysia, 2012 Aug;67(4):430-2.
    PMID: 23082459 MyJurnal
    The presence of cutaneous metastases in squamous cell carcinomas of the head and neck (SCCHN) is rare and associated with a dismal prognosis. It is vital to distinguish these lesions from direct invasion of the skin by SCCHN or primary cutaneous malignancies as the prognosis is vastly different and so is the management. In this case report, we present four cases of cutaneous metastases and also briefly review the literature pertaining to this phenomenon.
    Matched MeSH terms: Mouth Neoplasms/pathology*
  17. Ashazila MJ, Kannan TP, Venkatesh RN, Hoh BP
    Oral Oncol, 2011 May;47(5):358-64.
    PMID: 21450513 DOI: 10.1016/j.oraloncology.2011.03.005
    Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been documented as important events in oral squamous cell carcinoma (OSCC). Five microsatellite markers D3S192, D3S966, D3S647, D3S1228 and D3S659 were selected on chromosome 3p because of high frequency of alterations reported in head and neck squamous cell carcinoma and the involvement of von Hippel Lindau (VHL) at 3p25-26 and the fragile histidine triad (FHIT) at 3p14.2 genes proven in many tumour types. A total of 50 archival tissue samples of OSCC and corresponding normal samples were analyzed for LOH and MSI status. The overall LOH for the markers selected on 3p was 56 out of 189 informative cases (29.6%). The most frequent LOH was identified for the marker D3S966 which was 18/42 (42.8%) of informative cases suggesting the presence of putative tumour suppressor genes (TSGs) in this loci. In this study, high frequency of microsatellite instability was found in D3S966 which was 28.6% of informative cases; this reveals the possibility of mutations of MMR genes in this region. Frequent microsatellite alterations (MA) were observed in 3 markers D3S966 (71.4%), D3S1228 (56.7%) and D3S192 (41.0%). There was no significant association between LOH with gender, tumour stages and differentiation grades. However, there was a significant association between tumour stage and differentiation grades with MSI status in OSCC in Malaysian population with p values of 0.002 and 0.035, respectively. There was also a significant association between MA and differentiation grades (p=0.041).
    Matched MeSH terms: Mouth Neoplasms/pathology
  18. Saleh A, Zain RB, Hussaini H, Ng F, Tanavde V, Hamid S, et al.
    Oral Oncol, 2010 May;46(5):379-86.
    PMID: 20371203 DOI: 10.1016/j.oraloncology.2010.02.022
    Despite the advances in cancer treatment, the 5-year survival rate for oral cancer has not changed significantly for the past 40 years and still remains among the worst of all anatomic sites. Gene expression microarrays have been used successfully in the identification of genetic alterations in cancer development, however, these have hitherto been limited by the need for specimens with good quality intact RNA. Here, we demonstrated the use of formalin-fixed paraffin-embedded tissues in microarray experiments to identify genes differentially expressed between cancerous and normal oral tissues. Forty-three tissue samples were macrodissected and gene expression analyses were conducted using the Illumina DASL assay. We report RNA yield of 2.4 and 0.8 microg/mm(3) from tumour and normal tissues, respectively and this correlated directly with the tissue volume used for RNA extraction. Using unsupervised hierarchical clustering, distinct gene expression profiles for tumour and normal samples could be generated, and differentially expressed genes could be identified. The majority of these genes were involved in regulation of apoptosis and cell cycle, metastasis and cell adhesion including BCL2A1, BIRC5, MMP1, MMP9 and ITGB4. Representative genes were further validated in independent samples suggesting that these genes may be directly associated with oral cancer development. The ability to conduct microarrays on formalin-fixed paraffin-embedded specimens represents a significant advancement that could open up avenues for finding genes that could be used as prognostication and predictive tools for cancer.
    Matched MeSH terms: Mouth Neoplasms/pathology
  19. 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: Mouth Neoplasms/pathology*
  20. 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: Mouth Neoplasms/pathology
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