Molecular basis of opmds


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  • wide inter- and intra observer variability has been observed in assessments of the presence/absence and degree of this condition (7). A binary OED classification method was recently described, dividing them between lesions at low and high risk of malignant transformation. This could be used as a complementary method to improve the sensitivity and specificity offered by the 2005 system in current use
  • Lesions encompass histological continuum between normal and cancerous tissuesAtypia cellular levelThe malignant potential of oral precancerous lesions is assessed by histopathology and mainly based on the presence and degree of dysplasia in biopsy material
  • This histopathological grading of OED was designed to assist prediction of the malignant transformation of these lesions.certain cellular and tissue alterations are associated with malignancy and premalignancy.
  • An alarming morphological alteration of dysplastic epitheliumMany oral precancers show excess surface keratin (hyperkeratosis, hyperparakeratosis, hyperorthokeratosis) and most show hyperplasia of the spindle cell layer (acanthosis), but both changes are common to a number of mucosal lesions without a cancer transformation potential and neither is necessary to the diagnosis of dysplasia.
  • Normally the nucleus of basal cells is perpendicular to the basement membrane. When this arrangement is lost, the nuclei are in different angles. This is called loss of polarity
  • Bulge between the tapers to accommodate increased no. of cellsExtremely elongated rete processes with minimal cellular atypia are characteristic of hyperplastic conditions, including papillomavirus infections, frictional keratosis, psoriasis and pseudoepitheliomatous hyperplasia.
  • Premature production of keratin below the surface layer
  • However, It is difficult to determine the amount of basal cell hyperplasia in oral precancers because of transverse sectioning of tissue samples and because of the natural undulation of the inferior margin of squamous epithelium
  • enlarged nuclei (nuclear hyperplasia)dark-staining nuclei (hyperchromatism)enlarged, often eosinophilic nucleoli (prominent nucleoli)increased nuclear-to-cytoplasmic ratio(1:1)
  • two bands representing the two alleles (maternal and paternal) are seen in the normal tissue DNA. When only one band is seen in the sample DNA, then the other allele has been los, referred to as “loss of heterozygosity” (LOH), “allelic imbalance” (AI) or “allelic loss”.
  • 3p,9p; 8p,13q,17p______ p16@9p; p53@17pPathological and molecular progression of oral cancer; an adapted model. Underlying genetic instabilities include the loss of heterozygosity (LOH), amplification/ deletion orupregulation/ down-regulationof certain oncogenes or tumor-suppressor genes
  • Often a large area of oral epithelium exist that has been PRECONDITIONED for cancer by long term exposure to carcinogens. It has been found that the majority of oral squamous cell carcinomas, if not all, develop in precancerous lesions, macroscopically visible or not, also known as fields characterized by some of these specific genetic alterations.Thishypothesis could explain the development of multiple primary tumors and the frequent local recurrences in OSCC patients.In the initial phase, a stem cell acquires genetic alterations and forms a “patch”, a clonal unit of altered daughter cells. The conversion of a patch into an expanding field is the next logical and critical step in epithelial carcinogenesis. Additional genetic alterations are required for this step, and by virtue of its growth advantage, a proliferative field gradually displaces the normal mucosa. Ultimately, clonal divergence leads to the development of one or more tumors within a contiguous field of preneoplastic cells. The majority of these fields is not visible by clinical inspection. As mentioned above, only a minor subgroup of oral precancerous lesions can be seen clinically as leukoplakia or erythroplakia.
  • Microsatellites are small repetitive sequences that are highly polymorphic with respect to length in the population. Microsatellites, also known as Simple Sequence Repeats (SSRs) or short tandem repeats (STRs), are repeating sequences of 2-6 base pairs of DNA.[1] It is a type of variable number tandem repeat (VNTR). Microsatellites are typically co-dominant. They are used as molecular markers in genetics, for kinship, population and other studies. They can also be used for studies of gene duplication or deletion, marker assisted selection, and fingerprinting.Because this method can theoretically not discriminate loss of one allele over the gain of another, the term “allelic imbalance” is most correct.
  • fragile histidine triad;
  • They encode proteins involed in DNA repair processes like: base excision repair, nucleotide excision repair, mismatch repair, double strand break repair.
  • Telomere: repeat sequence of TTAGGG; activation of telomerase  dyskeratosiscongenita5  3; laggingokazaki pieces; RNA primer
  • The oral lesions consist of recurrent blisters, epithelial atrophy, and leukoplakiacharacterized by hyperpigmentation, atrophic skin areas, telangiectasia, nail dystrophy, hyperhidrosis, skin and mucosal bullae, blepharitis and ectropion, anemia
  • STRONG CARCINOGENS, such as polycyclic aromatic hydrocarbons (PAHs), nitrosamines and aromatic amines, occur in smaller amounts (1–200 ng per cigarette) than WEAK CARCINOGENS such as acetaldehyde (nearly 1 mg per cigarette). The total amount of carcinogens in cigarette smoke adds up to1–3 mg per cigarette (similar to the amount of nicotine, which is 0.5–1.5 mg per cigarette), although most of this consists of weaker carcinogenic agents such as acetaldehyde, catechol and isoprene. Carcinogens form the link between nicotine addiction and cancer. Carcinogenicity studies of nicotine have mostly been negativeMetabolic activation is generally initiated by cytochrome P450 enzymes (P450s)Nicotine and carcinogens can also bind directly to some cellular receptors, leading to activation of the serine threonine kinase AKT(also known as protein kinase B), protein kinase A (PKA) and other factors. This, in turn, can result in decreased apoptosis, increased angiogenesis and increased cell transformation. Tobacco products also contain tumour promoters and co-carcinogens, which could activate protein kinase C (PKC), activator protein 1 (AP1) or other factors, thereby enhancing carcinogenesis.
  • Nicotinic stomatitis, or smoker’s palatelesions are not premalignant !!!!!!
  • diffuse and poorly demarcated atrophic, erosive or keratotic plaques that may affect some parts of, or the entire vermilion border.
  • Results to date suggest that L1-based immunization may prevent the development of OSCC associated with HPV
  • This new herpesvirus shares several features with EBV. strongly linked with all forms of Kaposi's sarcoma, whether associated with HIV infection or not.
  • It is important to note that cofactors, such as tobacco, alcohol, carcinogens, and other viral infections (HIV tat protein, herpes simplex virus), may participate along with HPV in the transformation process to oral cancer development.
  • Graft-versus-host disease: erosion and white lesions that resemble lichen planus on the buccal mucosa
  • three sequential steps: conditioning regimen, donor T cell activation, and effector mechanisms. In step one, the conditioning regimen simultaneously damages and activates host tissues, amplifying antigen presentation to allogeneic donor T cells. In step two, donor T cells, activated by host alloantigens, proliferate and secrete a variety of cytokines. Type 1 cytokines (interleukin- 2 and interferon-g ) are critical for acute GVHD, but several regulatory mechanisms of tissue damage include inflammatory cytokines and cytolytic cellular effectors.Matching of the major histocompatibility complex (MHC) antigens speeds engraftment and reduces the severity of GVHD
  • well-defined central atrophic red area surrounded by a sharp elevated border of irradiating whitish striae (Fig. 69). Telangiectasia, petechiae, edema, erosions, ulcerations, and white hyperkeratotic plaques may be seen.
  • Interaction of sex, hormonal milieu, the HPA axis, and defective immune regulation, such as clearance of apoptotic cells and immune complexes, modify this susceptibility. The loss of immune tolerance, increased antigenic load, excess T cell help, defective B cell suppression, and shifting of Th1 to Th2 immune responses lead to cytokine imbalance, B cell hyperactivity, and the production of pathogenic autoantibodies.
  • 1–3 mg per cigarette
  • Molecular basis of opmds

    1. 1. Molecular basis of Oral Potentially Malignant Disorders Presented by: Ujwal Gautam BDS 2009(4th year) BPKIHS
    2. 2. Contents • • • • • • • • • • • • • Malignant Transformation Oral Epithelial Dysplasia Multistep Carcinogenesis Field Cancerization Molecular diagnosis Genes playıng role ın malignancy Role of growth factors Telomere and Cancer Role of Alcohol Role of Viruses Chronic Hyperplastic Candidiasis Graft Versus Host Disease Systemic Lupus Erythematosus
    3. 3. Malignant Transformation  multifactorial process  Genetic predisposition, immunodeficiency, diet and viral infections, e.g. HPV (human papillomavirus) and HHV (human herpes virus)
    4. 4. CANCEROUS lesion NORMAL tissue PREMALIGNANCY Histological connotation at tissue level  DYSPLASIA
    5. 5. Oral precancerous lesions are usually histologically classified by the presence or absence of Oral Epithelial Dysplasia (OED)
    6. 6. oral precancer grading criteria  the cellular atypia or dysplasia is similar to that seen in squamous cell carcinoma;  there is no evidence of invasion into underlying stroma (the diagnosis would then change to carcinoma)  the epithelium with the greatest proportion of atypical cells has the greatest risk of being or becoming a carcinoma;  the epithelium with the most extreme atypia of cells has the greatest risk of being or becoming a carcinoma;  the final grading or diagnosis should be based on the most severely involved area of change, even if that area includes no more than a few rete processes
    7. 7. Dysplastic features The malignant potential of oral precancerous lesions is assessed by histopathology and mainly based on the presence and degree of dysplasia in biopsy material. Not exclusive to carcinogenesis, as they may be seen in reactive epithelium or epithelium influenced by a variety of systemic alterations.
    8. 8. o Cells high in the epithelium have the same immature appearance as those in the basal layers. o due to an apparent inability to properly differentiate and mature from basal cells to prickle cells to flattened keratinocytes. o This feature is especially pronounced in severe epithelial dysplasia and carcinoma in situ.
    9. 9. o Drop-shaped rete processes, regardless of their size, especially if secondary projections or nodules are seen to arise from the basal layer and branch at in different angles into the lamina propria and connective tissue papillae are suggestive of poor prognosis.
    10. 10. o Enlarged, tripolar or star-shaped mitotic figures (abnormal mitoses), however, are much more indicative of precancerous changes. o Abnormal mitosis may also be defined as mitotic figures found in unusual locations above the basal cell layer.
    11. 11. o much more commonly seen in oral carcinomas than in oral premalignancies. o dyskeratosis may be represented by individually keratinized cells or by tight concentric rings of flattened keratinocytes (epithelial pearls).
    12. 12. o loss of cellular cohesiveness (acantholysis) are major signs of poorly differentiated carcinoma but are extremely rare in the epithelial dysplasia of oral precancer. o When present, these features must be distinguished from intercellular edema, intraepithelial inflammatory cells and degenerating cells with pyknotic nuclei and vacuolated cytoplasm
    13. 13. o Basal cell hyperplasia is of major importance to the diagnosis as well as to the grading of dysplasia
    14. 14. Multistep Carcinogenesis – Denotes the accumulation of genetic and/or epigenetic changes resulting in the progression from a normal cell into a cancer cell. – changes may appear in less important regions of the genome and are therefore a mere reflection of the genetic instability of the tumors, but some of these alterations specifically occur in genes that play a crucial role in signalling pathways that regulate DNA maintenance, cell cycle or other important physiological processes.
    15. 15. Genetic progression model for OSCC
    16. 16. Field Cancerization A model for field cancerization
    17. 17. Molecular diagnosis The hypothesis that oral cancers are preceded by precancerous fields of genetically altered cells, suggests that screening approaches for precancerous changes might become an option with molecular tools detecting genetic alterations As the fields are characterized by genetic changes, the markers of choice include;
    18. 18. Molecular diagnosis I. Numerical chromosomal alterations II. Allelic imbalance analysis by microsatellites Chromosomal changes in (pre)cancer cells can be determined by allele-specific markers such as microsatellites. The loss of a given marker is generally considered a hallmark of the loss of a specific chromosomal locus harboring a tumor suppressor gene, or an unbalanced amplification. III. DNA content: Abnormal nuclear DNA content (aneuploidy) is an indicator of chromosomal aberrations and is associated with malignant and premalignant lesions
    19. 19. Genes playıng role ın malignancy • Oncogenes • Tumor suppressor genes • DNA repair genes 23
    20. 20. What are the genes responsible for tumorigenic cell growth? Normal Proto-oncogenes Tumor suppressor genes + - Cell growth and proliferation Cancer Mutated or “activated” oncogenes Loss or mutation of Tumor suppressor genes ++ Malignant transformation 24
    21. 21. Genes playıng role ın malignancy ONCOGENES • Oncogenes are mutated forms of cellular proto-oncogenes. • Proto-oncogenes code for cellular proteins which regulate normal cell growth and differentiation.  p21 ras oncoprotein has been observed in precancers 25
    22. 22. Genes playıng role ın malignancy TUMOR SUPPRESSOR GENES • • • Normal function  inhibit cell proliferation Absence/inactivation of inhibitor cancer Both gene copies must be defective for loss of function     p53 gene Rb gene p16INK4A FHIT 26
    23. 23. Genes playıng role ın malignancy DNA REPAIR GENES These are genes that ensure each strand of genetic information is accurately copied during cell division of the cell cycle. Mutations in DNA repair genes lead to an increase in the frequency of mutations in other genes, such as proto-oncogenes and tumor suppressor genes. Eg. Defect in the genes encoding proteins involved in nucleotide-excision repair of damaged DNA causes Xeroderma pigmentosum. 27
    24. 24. Genes playıng role ın malignancy Importance of DNA repair 28
    25. 25. Role of growth factors Growth factors necessary for normal growth and development may also play a role in oral cancer and precancer. Fibroblast grown factors (FGF) – widely distributed in normal and neoplastic tissues – involved in angiogenesis and wound healing, and have also been shown to be mitogenic for keratinocytes. – Almost all oral carcinomas are immunoreactive to FGF and oral carcinoma cells in culture are capable of expressing FGF. – Biopsy samples of oral dysplastic lesions have also demonstrated positive focal staining which becomes stronger with increasing immaturity or severity of the dysplastic cells.
    26. 26. Epidermal growth factor receptor (EGFR) – protein of the proto-oncogene c-erb – Its expression has been correlated somewhat with an increased rate of recurrence in some cancers of the head and neck region – Role in oral precancers has not yet been proven Proliferation markers – measure of its biological potential, proliferative activity, can be measured by immunohistochemical demonstration of proliferation markers such as proliferating cell nuclear antigen (PCNA) or the nonhistone nuclear protein, Ki67 (MIB 1) – Local recurrence has been associated with a decreased PCNA expression or increased Ki67 expression in head and neck cancers – evaluation of these events in oral precancers has not yet been reported.
    27. 27. Telomere and Cancer
    28. 28. Telomere and Cancer
    29. 29. Role of Tobacco carcinogens contained in tobacco products are responsible for cancers. More than 60 carcinogens are in cigarette smoke and at least 16 in unburned tobacco. Among these, tobacco-specific nitrosamines (such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N′nitrosonornicotine (NNN)), polycyclic aromatic hydrocarbons (such as benzo[a]pyrene) and aromatic amines (such as 4-aminobiphenyl) seem to have an important role as causes of cancer.
    30. 30. Role of Tobacco • • PAH,NNK and NNN are the most likely causes of oral cancer in smokers. NNK and NNN, perhaps together with enhancing agents, are the carcinogens most likely to cause oral cancer in smokeless-tobacco users. ORAL CANCER
    31. 31. Role of Tobacco Smokeless tobacco keratosis – characterized by a intracellular vacuolization or "edema" of superficial layers, perhaps interspersed with streaks of parakeratinized cells. – most likely results from a low-grade chemical burn from the alkaline tobacco used. It has been referred to as surface etching and has no implications one way or another relative to the risk of malignant transformation
    32. 32. Role of Tobacco Reverse Smoker’s Palate – benign hyperkeratosis and acanthosis to hyperkeratosis accompanied with graded epithelial dysplasia or invasive squamous cell carcinoma. – Cigarette smoke causes oxidative damage, probably because it contains free radicals such as nitric oxide and mixtures of hydroquinones, semiquinones and quinones, which can induce redox cycling
    33. 33. Role of Alcohol – an important risk factor for the development of OSCC – Metabolism of ethanol results in the generation of toxic compounds such as acetaldehyde, hydroxyethyl radicals, ethoxy radicals, and hydroxy radicals – Acetaldehyde is highly toxic, mutagenic, and carcinogenic – In the mouth the conversion of alcohol to acetaldehyde can be catalyzed by alcohol dehydrogenase (ADH) enzymes from the epithelium and also from oral microorganisms. – Acetaldehyde in the oral cavity can also come from tobacco smoking. Tobacco smoke contains toxic aldehydes, and the combined use of tobacco and alcohol has a synergistic effect on the risk of developing oral cancer
    34. 34. Actinic Cheilitis and Role of UV radiation Result of clonal expansion of UVB-induced transformed keratinocytes characterised by molecular and genomic alterations causing genomic instability Though additional genetic changes are necessary for full malignant transformation with the potential for invasiveness and metastasis. UVB from the sun leads to mutations in the epithelial p53 tumoursuppressor gene that result in the dysregulation of its functions. Formation of aberrant covalent bonds between adjacent cytosine bases in epithelial DNA.
    35. 35. Role of Viruses With latent or chronic infections, the viral agent becomes incorporated into the human, immortalize the host cell, and facilitate malignant transformation; 1. Viral interference with tumor suppressor gene function 2. Viruses may act as vectors for mutated proto-oncogenes (oncogenes). Overexpression of these oncogenes in viral-infected cells
    36. 36. Role of Viruses Pathogenesis: Oncoproteins, E6 and E7, from these viruses bind with wild-type p53 and pRb proteins and remove their ability to stimulate DNA repair or apoptosis. Viral-infected cells may continue to undergo additional mutations induced by other `DNA-damaging' events, including tobacco, alcohol, carcinogens, toxins, ionizing radiation, prolonged ultraviolet light/sun exposure, chemical insult, other viral infections, which may result in the development of a malignant tumor (transformation process).
    37. 37. Role of Viruses Human herpes virus 4 (HHV-4, Epstein- Barr virus) – allow immortalization of epithelial cells and B lymphocytes – EBV latent infection is capable of inducing malignant tumor formation in oncogenic genes. – EBV nuclear antigens (EBNA1, EBNA2, LMP1) are themselves known to be oncogenic while another EBV nuclear antigen (EBNA-LP) interferes with wild type p53 and pRb function and results in dysregulation of the cell cycle.
    38. 38. Role of Viruses Human herpes virus 8 (HHV-8, Kaposi's sarcoma- associated herpes virus, KSHV) – Has oncogenic (transforming) ability via a viral encoded receptor (G-protein coupled receptor), which induces cell proliferation mediated by vascular endothelial growth factor. – In addition, ras/raf oncogenes are activated by a proliferation cascade initiated by HHV-8. – Additional oncogenic proliferation factors, prad-1, and bcl-2, expressed by HHV-8 interfere with wild-type p53 and wild-type pRb regulation of cell proliferation.
    39. 39. Role of Viruses Human herpes virus 6 (HHV-6) – Tumor necrosis factor-alpha is over expressed and this appears to induce HIV replication which in turn increases HIV tat protein, a protein with oncogenic potential. – In both immunocompetent and immunosuppressed hosts, HHV-6 produces an oncogenic protein (ORF-1) which binds to wild-type p53 and inhibits regulation of cell proliferation, which allows for the escape of HHV-6 infected host cells from cell growth regulation
    40. 40. Role of Viruses Human papilloma virus (HPV) have tropism for squamous cells and their full reproductive life cycle is only supported in these epithelial cells as their viral replication functions are limited to the most terminally differentiated squamous cells or keratinocytes. viral DNA synthesis occurs within the basal layer of squamous epithelium and the incorporation of HPV genes into the basal cells ensures that a persistent lesion will develop.
    41. 41. Role of Viruses HPV as an etiologic factor for OSCC Gene products E5, E6 and E7, are considered to be oncoproteins and are associated with the development of squamous cell carcinoma of the oral cavity. 1. E6 and E7 mediated inhibition of cell cycle regulation tumor suppressor genes 2. E5 mediated stimulation of growth factor activity, which enhances cell proliferation and may influence transformation to a malignant process.
    42. 42. Role of Viruses HPV Cofactors Squamous papillomas 6, 11 Verruca vulgaris 1, 2, 4, 7, 57 Alcohol, carcinogen Smoking, HSV, HIV focal epithelial hyperplasia (Heck's disease) 13, 32 Condyloma acuminatum 2, 6, 11, 16, 18, 31, 33, 35 Oral epithelial dysplasia (koilocytic dysplasia) 16, 18, 31, 33, 35 verrucous carcinoma 2, 6, 11, 16, 18 squamous cell carcinoma 2, 3, 13, 16, 18, 31, 33, 35, 52, 57
    43. 43. Role of Viruses Herpes simplex virus (HSV) – binds and inactivates basic fibroblastic growth factor, activating certain oncogenes (c-myc) that results in the activation, amplification and overexpression of pre-existing oncogenes within neoplastic tissue, such as c-erb-B-1 and c-myc. – HSV participates in malignant transformation as a cofactor in squamous cell carcinoma development. – Possible reactivation of HSV infection(hit and run effect) by suppression of natural killer lymphocyte activity due to chromosomal aberration/mutations and gene amplification in the presence of ultraviolet light and carcinogens (nitrosamine and other tobacco extracts)
    44. 44. Chronic Hyperplastic Candidiasis • CHC is a form of oral candidiasis that typically presents as an adherent chronic white patch on the commissures of the oral mucosa • It is characterized by hyphal invasion of the epithelial surface, which usually becomes parakeratinized; the hyphae rarely extend beyond the parakeratin layer. • Candida albicans is the most common Candida species present in candidal leukoplakia • Candida infection in oral leukoplakias was originally termed ‘candidal leukoplakia’ but it was rather turned down since Leukoplakia is itself known to be idiopathic.
    45. 45. It has been shown that leukoplakia with candidal infection has a higher rate of malignant transformation than uninfected leukoplakia, with estimates that 15% of non-dysplastic CHC will progress to dysplastic lesions with 10% of these developing OSCC
    46. 46. Attributes of C. albicans that may influence oral cancer development – – – – – Colonization of the epithelium Ability to produce carcinogens and initiate carcinogenesis Ability to promote carcinogenesis in initiated epithelium Ability to metabolize procarcinogens Ability to modify the microenvironment and induce chronic inflammation
    47. 47. Production of Carcinogens Candida might induce OSCC by directly producing carcinogenic compounds like nitrosamines which binds with DNA to form adducts with bases, phosphate residues, and/or hydrogen bonding sites that could cause miscoding or irregularities with DNA replication. Point mutations thus induced may activate specific oncogenes and initiate the development of oral cancer. C. albicans has been shown to act as a promoter of oral carcinogenesis in rat and mouse OSCC models In vitro, C. albicans cultures have shown metabolism of ethanol to the carcinogenic acetaldehyde which is highly toxic, mutagenic, and carcinogenic
    48. 48. Induction of Chronic Inflammation C. albicans has been shown to secrete specific proteinases, capable of degrading basement membrane and extracellular matrix. Degradation of laminin-332, a laminin present in the basement membrane associated with oral epithelium, by C. albicans has been described. C. albicans has also been demonstrated to degrade E-cadherin, a transmembrane glycoprotein important in adhesion of adjacent keratinocytes Mucosal bacterial infection will induce chronic inflammation in the adjacent connective tissue leading to upregulation of cytokines and growth factors, which in turn may influence carcinogenesis
    49. 49. Graft Versus Host Disease The pathogenesis of acute graft versus host disease (GVHD) is multistep process. GVHD occurs in three sequential steps:  conditioning regimen: simultaneous damage and activation of host tissues, amplification of antigen presentation to allogeneic donor T cells.  donor T cell activation by host alloantigens, proliferation and secretion of a variety of cytokines, Type 1 cytokines (interleukin- 2 and interferon-γ) and  effector mechanisms.
    50. 50. Systemic Lupus Erythematosus characterised by a myriad of immune system aberrations involves B cells, T cells, and cells of the monocytic lineage, resulting in polyclonal B cell activation, increased numbers of antibody producing cells, hypergammaglobulinaemia, autoantibody production, and immune complex formation results in primary pathological findings of inflammation, vasculitis, and vasculopathy
    51. 51. APOPTOSIS AND SLE Defective apoptosis in SLE leads to the prolonged survival of pathogenic lymphocytes Under normal circumstances, apoptotic cells are engulfed by macrophages in the early phase of apoptotic cell death without inducing inflammation or the immune response. However, the clearance of apoptotic cells by macrophages in patients with SLE is impaired. This is not confined to monocytes and macrophages of the peripheral blood, but also occurs in the germinal centres of lymph nodes.
    52. 52. Multiple Choice Questions Which of these is associated with significant risk of malignant transformation? a. b. c. d. HSV 1,3 HPV 8, 10 HPV 16, 18 CVA 16
    53. 53. Multiple Choice Questions The current “gold standard” for predicting the malignant potential of the precancerous lesions is the a. b. c. d. presence & degree of dysplasia presence of candidal hyphae presence of red areas in the lesion site of the lesions
    54. 54. Multiple Choice Questions Which stage of syphilis is a pre-disposing condition to oral cancer? a. b. c. d. Primary stage Secondary stage Tertiary stage Syphilis is not a pre disposing condition to oral cancer
    55. 55. Multiple Choice Questions The total amount of carcinogens in cigarette smoke adds up to a. b. c. d. 1-3 mg per cigarette 7-8 ug per cigarette 1-2 ng per cigarette Recent studies show tobacco smoke contains no carcinogen
    56. 56. Multiple Choice Questions Which of these is not a Tumor Suppressor gene? a. b. c. d. p53 p16INK4A YNWA Rb
    57. 57. References • • • • • • • • • • • • Sivapathasundharam B., Rajendran R.; Shafer’s Textbook of Oral Pathology, 7/e, Elsevier, 2012 Greenberg M., Glick M., Ship j. A., Burket's Oral Medicine , 11/e, BC Decker Inc, 2008 Satyanarayana U., Chakrapani U.; Biochemistry; 3/e; Books and Allied P Ltd; 2006 Wight A. J., Ogden G. R.; Possible mechanisms by which alcohol may infuence the development of oral cancer: a review; Oral Oncology 34 (1998) 441-447 Warnakulasuriya S., Johnson N. W., Waal I.; REVIEW ARTICLE: Nomenclature and classification of potentially malignant disorders of the oral mucosa; J Oral Pathol Med (2007) 36: 575–80 Neville B. W., day T. A.; Oral Cancer and Precancerous Lesions; CA Cancer J Clin 2002;52:195215 Mok C C, Lau C S; Pathogenesis of systemic lupus erythematosus; J Clin Pathol 2003;56:481– 490 Wood, Khammissa, Meyerov, Lemmer, Feller; Actinic Cheilitis: A Case Report and a Review of the Literature; European Journal of Dentistry; January 2011 - Vol.5 Ferrara J. L. M.; Pathogenesis of Acute Graft-Versus-Host Disease: Cytokines and Cellular Effectors; Journal Of Hematotherapy & Stem Cell Research 9:299–306 (2000) Pagano, Blaser, Buendia, Damania, Khalili; Infectious agents and cancer: criteria for a causal relation; Seminars in Cancer Biology 14 (2004) 453–471 Sitheeque M.A.M., Samaranayake L.P. ; Chronic Hyperplastic Candidosis/Candidiasis (Candidal Leukoplakia); Crit Rev Oral Biol Med 14(4):253-267 (2003) Flaitz a C.M. , Hicks M.J.; Molecular piracy: the viral link to carcinogenesis; Oral Oncology 34 (1998) 448- 453