An Overview of the Prevention of Oral Cancer and Diagnostic Markers of Malignant Change : Markers of Value in Tumor Diagnosis 1

IntroductionStaging : Assess Prognosis -Most Widely Used Classification : TNM Staging (By IUAC)Modificaion : STNMP S: Site P:PathologyNodal Involvement : Most Crucial to Prognosis

IntroductionPathologic finding - Morphological ChangesMorphological change 1.epithelial abnormality : proliferation, maturation, differentiation 2.Invasion to adjacent tissue

Prognostic Factors1.Morphology-most reliable indicator of malignancy(Weakpoint: subjective interpretation)-presence of DYSPLASIA2.Depth of the lesion -8mm or more : Poor prognosis3.Pattern of Invasion4.Nodal spreading

Carcinogenesis :Multistep ProcessGenetic damage - at Initiation,Promotion,ProgressionInitiation :Irreversible genetic damage CAUSE - Chemical carcinogen - Radiation - Virus

Carcinogenesis :Multistep ProcessMALIGNANCY : Promotion and Progression involve further genetic alterationClonal Expansion of Malignant Cell:Local invasion and distant metastasisMutations of Tumor suppressor Gene : p53

Carcinogenesis :Multistep ProcessHost Factor - age - inheritance - humoral immunity - cellular immunityIdentification of genetic mutation - screening High-risk Group

Gene Study DNA,RNA,ProteinPCR : amplifying DNA sequenceSouthern blotting : DNA analysisNorthern blotting : RNA analysisWestern blotting : Protein analysis In situ hybridization : direct analysis of DNA or RNAImmunohistochemistry : applying antibodies to tissue section most readily available technique

Identification of Tumor Markers- Oncogenes and Tumor suppressor GenesOncogene: mutated or overexpressed version of normal gene - converting normal cell to tumor cellGenetic fingerprint of dysplastic and cancer cell : Identical - Dysplastic lesion ; precursor lesion or spread locally

Tumor suppressor gene- p53Expression : response to damaged DNA p53 protein : stops cell cycle allow for DNA repairApoptosis : failure in DNA repairMutation of the Tumor Suppressor gene : failure in apoptosis and allow for mutated cell surviving

Detection of p53 proteinAnti-p53 antibody - identification is frequently associated with mutationSuggestive of malignancyException : wild type p53, altered detection threshold false positive

Mutagen sensitivityLatent or hidden chromosomal instabilitySensitivity of PBL to bleomycin -induction of chromatid breaksHigh mutagen sensitivity : greater risk of developing multiple primary tumors

Proliferation MarkerRapid growth : Poor prognosis Ki-67 : detect antigen expressed by cells that are in G1,S1,G2,MPCNA : cell replication and DNA repairAgNORs : nucleolar organizing regions that take up silver

DNA contents of TumorAneuploidy : alteration in the number of chromosomePloidy : using flow cytometry , static cytometry, image cytometryPoor prognosis associated with aneuploid tumor

Cell surface antigenIntegrin, Cadherin/catenin complex -prime mediators of cell adhesion in normal and transformed cellsLoss of control : promote neoplastic change

CytokeratinBest markers of malignancy : -K8,K18,K19 (simple) - Keratin 10,13 (secondary markers) Keratin 16,19 : predictive of an increased tumor developmentDetermine prognosis of tumor

Stromal Change Prognosis of tumor : microvascularityCD31,vWF ; various antigen in endothelial cellMicrovascular volume : related to tumor prognosisExfoliative CytologyUsing microscopyAssessment of changes of morphometry

SummaryDiagnosis of oral cancer : Histomorphological analysis supplemented by the study of immunohistochemical and molecular biological techniquesExpection : using morphological and molecular profiling in detection and treat the oral cancer