Biology of Neoplasia

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• Neoplasm: Cellular phenomenon seen in complex organisms, which altered cells show autonomous growth and form clonal and multicellular masses. Tumour: Named after tissue of origin

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• Age: Lifetime risk in 1 in 3.5, 25% of all deaths in NSW Disease of older people.

1. Risk Factors

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   • Tobacco Smoking Drinking alcohol Diet of low fruit and vegetables Physical inactivity Obesity Sexual transmission of HPV

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• Key Features: Clonality and Tumour Heterogeneity Cancer cells have developed mechanisms to evade phagocytosis and breakdown. Like a 'dominant' cell. Consequences are: 1. Altered Growth 2. Altered cellular differentiation 3. Change in relationship to surrounding cells and tissues.

1. Growth of Tumours

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   • Refers to the balance of rate of cellular replication and cellular death. Affected by the percentage of cells within cellular cycle, sensitivity to apoptosis and the capacity to avoid cellular senescence.
2. Altered Cellular Differentiation

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   • Differentiation is the extent to the tumour cells resemble the cells from which it was derived. Variable loss of differentiation is a typical finding in neoplasm. Seen in individual cells or tissues. The morphology reflects the biological changes such as, Genetic instability reflects nuclear abnormalities, altered growths such as change in mitotic rate, altered differentiation changed in changes in cytoplasm.
3. Changes in Relationship to surrounding cells and Tissue

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   • Change in epithelial organisation. A neoplastic (adeno/adenocarcinoma) will present itself like a change in epithelial such as a columnar to a squamous or a cuboidal. Loss of differentiation can be viewed or manifest as a changes in epithelial organisation. The loss of differentiation present itself in a weird blob..Induction of Stroma: As tumours grow, it induces stroma such as increases of blood vessels and connective tissues, The body often responded by forming scar tissue.Tissue invasion and spread: Extension of the neoplasm into the surrounding tissue... Benign tissues do not invade, malignant tumours may invade.

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• It may metastasised in the brain and increase pressure in head and cause death

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• May spread to the lungs and other sites of the body

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• It spread via lymphatic or haematogenous system. Sometime it spread via transcavitatory or implantation.

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• Pathological Diagnosis can be done from incision/excision/core needle biopsy which are core histopathological examination. Cytopathological examination can also be done.

1. Predicting outcomes

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   • Assessment can be done by histopathological classification, grading, or biological assessment. Clinicopathological staging, for T,N,M stages give overall stages which is the most important predictor of outcome in malignancy.

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• Other factors includes chemicals either exogenous or endogenous Viruses Sucha s Human papilloma virus(HPV) which involves squamous neoplasms of mucosal surfaces. Hepatitis B virus: Hepatocellular carcinoma Ionising radiationTobacco smoking

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• Medelian inheritance of cancer: Predisposition of genes accounts for less than 5% of the cancers Indirect or polygenic effects on cancer development are largely unknown

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• Molecular changes, includes loss of tumour suppressor genes loss or silencing, it also could be due to oncogenes activation. It results in loss of genomic integrity also loss of control of cell cycle. Phenotypic changes (survival of the fittest hypothesis).

1. Molecular Changes

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   • Genetic: nucleotide mutation, deletions or truncations. Chromosomal translocation or gene amplification. Epigenetic could also had promoter methylation or other causes.
2. Oncogenes

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   • Genes that cause cancer. Changed genes that are normally involved in cellular growth. It also acts in a dominant fashion
   1. K-ras activation by point mutation?!
3. Tumour Suppressor genes

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   • Loss of TSG induces cancer, it acts in a recessive fashion and often involves in control of DNA integrity... Examples includes Rb, p53 or MLH1