Week 8 Neoplasia 2 PDF

AHBS 2319 BASIC PATHOLOGY Week 8  Week 8 Reference: Kumar et al. (2018), Robbins Basic Pathology, p189-p242.  Classification, Nomenclature, Epidemiology Neoplasia : “New growth” Neoplasm is often referred to as a tumor The study of tumors is call oncology (oncos = tumor,...

AHBS 2319 BASIC PATHOLOGY Week 8  Week 8 Reference: Kumar et al. (2018), Robbins Basic Pathology, p189-p242.  Classification, Nomenclature, Epidemiology Neoplasia : “New growth” Neoplasm is often referred to as a tumor The study of tumors is call oncology (oncos = tumor, logos = study of) Cancer is the common term for all malignant tumors. Classification, Nomenclature, Epidemiology Benign tumor : Benign tumor of mesenchymal tissue The suffix “-oma” to the cell of the origin -Fibroblastic cell = fibroma -Lipid cell = lipoma -Smooth muscle = leiomyoma Classification, Nomenclature, Epidemiology Benign tumor : Benign tumor of epithelial tissue Based on their cells of origin & microscopic architecture  Classification, Nomenclature, Epidemiology Benign tumor of epithelial tissue Adenoma (based on origin of cell) -benign epithelial neoplasm that forms grandular patterns. -tumors derived from glands  Classification, Nomenclature, Epidemiology Benign tumor of epithelial tissue Papilloma (based on microscopic architecture) -benign neoplasm -microscopically visible finger-like projections  Classification, Nomenclature, Epidemiology Benign tumor of epithelial tissue Polyp -neoplasm produces a macroscopically visible projections above a mucosal surface. -polyp preferably is restricted to benign tumor. Classification, Nomenclature, Epidemiology Malignant tumor: Malignant tumor of mesenchymal tissue -are usually called sarcoma -sarcoma =“Fleshy tumor” -Fibroblastic cell = fibrosarcoma -Lipid cell = liposarcoma -Smooth muscle = leiomyosarcoma Classification, Nomenclature, Epidemiology Malignant tumor: Malignant tumor of epithelial tissue -are called carcinoma -Squamous cell carcinoma (Squamous cell type) -Adenocarcinoma (Grandular growth pattern) Classification, Nomenclature, Epidemiology Teratoma (Dermoid cyst) -made up of variety of parenchymal cell types. -arise from totipotential cells -is a benign type Classification, Nomenclature, Epidemiology Inappropriate nomenclature Melanoma = CA of melanocyte Seminoma = CA of testicular origin Hepatoma = CA of hepatocyte Lymphoma = CA of lymphoid tissue Leukemia = CA of hematopoietic cells  Classification, Nomenclature, Epidemiology Characteristics of Benign and Malignant Neoplasm Features: Differentiation and anaplasia, local invasion, metastasis  Classification, Nomenclature, Epidemiology Differentiation and anaplasia Well differentiated tumors - Cells is resemble normal morphology of original tissue - In general, benign tumors are well differentiated cells  Classification, Nomenclature, Epidemiology Poorly differentiated or undifferentiated tumors - This anaplasia is marked by a number of morphologic & functional changes, it is a hallmark of malignant transformation. - Lack of differentiation.  Classification, Nomenclature, Epidemiology Anaplasia: A condition of cells in which they have poor cellular differentiation, losing the morphological characteristics of mature cells.  Classification, Nomenclature, Epidemiology Local Invasion Well differentiated tumors - Cells is resemble normal morphology of original tissue - In general, benign tumors are well differentiated cells Classification, Nomenclature, Epidemiology  Classification, Nomenclature, Epidemiology Metastasis Well differentiated tumors - Cells is resemble normal morphology of original tissue - In general, benign tumors are well differentiated cells Classification, Nomenclature, Epidemiology Classification, Nomenclature, Epidemiology Classification, Nomenclature, Epidemiology  Classification, Nomenclature, Epidemiology Epidemiology of Cancer - The incidence of cancer varies with age, geographic factors and genetic background. - The geographic variation in cancer incidence results mostly from different environmental exposures. - Cancer can occur at any age, but is most common in older adults.  Classification, Nomenclature, Epidemiology Statistics at a Glance: The Burden of Cancer in the United States In 2018, an estimated 1,735,350 new cases of cancer will be diagnosed in the United States and 609,640 people will die from the disease. The most common cancers (listed in descending order according to estimated new cases in 2018) are breast cancer, lung and bronchus cancer, prostate cancer, colon and rectum cancer, melanoma of the skin, bladder cancer, non-Hodgkin lymphoma, kidney and renal pelvis cancer, endometrial cancer, leukemia, pancreatic cancer, thyroid cancer, and liver cancer. The number of new cases of cancer (cancer incidence) is 439.2 per 100,000 men and women per year (based on 2011–2015 cases). The number of cancer deaths (cancer mortality) is 163.5 per 100,000 men and women per year (based on 2011–2015 deaths).  Classification, Nomenclature, Epidemiology Cancer mortality is higher among men than women (196.8 per 100,000 men and 139.6 per 100,000 women). When comparing groups based on race/ethnicity and sex, cancer mortality is highest in African American men (239.9 per 100,000) and lowest in Asian/Pacific Islander women (88.3 per 100,000). In 2016, there were an estimated 15.5 million cancer survivors in the United States. The number of cancer survivors is expected to increase to 20.3 million by 2026. Approximately 38.4% of men and women will be diagnosed with cancer at some point during their lifetimes (based on 2013–2015 data). In 2017, an estimated 15,270 children and adolescents ages 0 to 19 were diagnosed with cancer and 1,790 died of the disease. Estimated national expenditures for cancer care in the United States in 2017 were $147.3 billion. In future years, costs are likely to increase as the population ages and cancer prevalence increases. Costs are also likely to increase as new, and often more expensive, treatments are adopted as standards of care. Classification, Nomenclature, Epidemiology Statistics at a Glance: The Burden of Cancer Worldwide Cancer is among the leading causes of death worldwide. In 2012, there were 14.1 million new cases and 8.2 million cancer-related deaths worldwide. 57% of new cancer cases in 2012 occurred in less developed regions of the world that include Central America and parts of Africa and Asia; 65% of cancer deaths also occurred in these regions. The number of new cancer cases per year is expected to rise to 23.6 million by 2030.  Classification, Nomenclature, Epidemiology Cancer Statistics 2018 - Worldwide - Malaysia  Classification, Nomenclature, Epidemiology Epidemiology of Cancer - Environmental factors implicated in carcinogenesis include infectious agents, smoking, alcohol, diet, obesity, reproductive history and exposure to carcinogens.  Classification, Nomenclature, Epidemiology Epidemiology of Cancer - Cancer risk rises in certain tissues in the setting of increased cellular proliferation caused by chronic inflammation or hormonal stimulation.  Classification, Nomenclature, Epidemiology Epidemiology of Cancer - Epithelial cells lining may develop morphologic changes that signify an increased risk for developing cancer; such lesions are referred to as precursor lesions.  Classification, Nomenclature, Epidemiology Epidemiology of Cancer - The risk for developing cancer is modified by interactions between environmental exposures and genetic variants.  Mechanism and Causes of Neoplasia Cancer Genes  Oncogenes  Tumor suppressor genes  Genes that regulate apoptosis  Genes that regulate interaction between tumor cells & host cells Cancer is caused by certain changes to genes, the basic physical units of inheritance.  Mechanism and Causes of Neoplasia Cancer Genes Oncogenes = genes that induce a transformed phenotype when expressed in cells by promoting increased cell growth. Oncogenes are mutated/overexpressed of normal cellular genes = proto-oncogenes  Mechanism and Causes of Neoplasia Cancer Genes Tumor suppressor genes = genes that normally prevent uncontrolled growth, when mutated allow the transform phenotype to develop.  Mechanism and Causes of Neoplasia Carcinogenesis Process by which normal cells are transformed into cancer cells Mechanism and Causes of Neoplasia  Mechanism and Causes of Neoplasia Carcinogenesis  Mechanism and Causes of Neoplasia Carcinogenesis  Mechanism and Causes of Neoplasia Carcinogenesis  Mechanism and Causes of Neoplasia Carcinogenesis  Mechanism and Causes of Neoplasia Hallmarks of Cancer All cancers display 8 fundamental changes in cell physiology, which are considered the hallmarks of cancer: Self-sufficiency in growth signals Insensitivity to growth-inhibitory signals Altered cellular metabolism Evasion of apoptosis Limitless replicative potential (immortality) Sustained angiogenesis Invasion and metastasis Evasion of immune surveilance  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Self-sufficiency in growth signals Proto-oncogenes: normal cellular genes whose products promote cell proliferation. Oncogenes: mutant or overexpressed versions of proto- oncogenes that function autonomous without a requirement for normal growth-promoting signals  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Self-sufficiency in growth signals Oncoproteins promote uncontrolled cell proliferation by several mechanisms:  Stimulus independent of growth factor and its receptor, setting up an autocrine loop of cell proliferation ( PDGF-PDGF receptor in brain tumors)  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Self-sufficiency in growth signals  Mutations in genes encoding growth factor receptors or tyrosine kinases leading to constitutive signaling.  Amplification of EGF receptor family genes such as HER2 in breast cancer.  Fusion of portions of the ABL tyrosine kinase gene and the BCR protein gene, creating a BCR-ABF fusion gene encoding a constitutively active tyrosine kinase, in certain leukemias  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Self-sufficiency in growth signals  Mutations in genes encoding signaling molecules  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Self-sufficiency in growth signals  RAS commonly is mutated in human cancers and normally flips between resting GDP-bound state and active GTP-bound state; mutations block hydrolysis of GTP to GDP, leading to unchecked signaling.  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Self-sufficiency in growth signals  Overproduction or unregulated activity of transcription factors  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Self-sufficiency in growth signals  Translocation of MYC in some lymphomas leads to overexpression and unregulated expression of its target genes controlling cell cycling and survival  Mutations that activate cyclin genes or inactivate negative regulators of cyclins and cyclin-dependent kinases.  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Insensitivity to Growth Inhibitory Signals: Tumor Suppressor Genes RB: Governor of the Cell Cycle  Like other tumor suppressor genes, both copies of RB must be dysfunctional for tumor development to occur.  In cases of familial retinoblastoma, one defective copy of the RB gene is present in the germline, so that only one additional somatic mutation is needed to completely eliminate RB function. Mechanism and Causes of Neoplasia Mechanism and Causes of Neoplasia  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Insensitivity to Growth Inhibitory Signals: Tumor Suppressor Genes TP53: Guardian of the Genome  TP53 encodes p53, the central monitor of stress in the cell, which can be activated by anoxia, inappropriate oncogene signaling, or DNA damage. Activated p53 controls the expression and activity of genes involved in cell cycle arrest, DNA repair, cellular senescence, and apoptosis.  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Insensitivity to Growth Inhibitory Signals: Tumor Suppressor Genes TP53: Guardian of the Genome  DNA damage leads to activation of p53 by phosphorylation. Activated p53 drives transcription of CDKN1A (p21), which prevents RB phosphorylation, thereby causing a G1-S block in the cell cycle. This pause allows the cells to repair DNA damage.  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Insensitivity to Growth Inhibitory Signals: Tumor Suppressor Genes TP53: Guardian of the Genome  If DNA damage cannot be repaired, p53 induces cellular senescence or apoptosis.  Of human tumors, 70% demonstrate biallelic mutations in TP53.  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Insensitivity to Growth Inhibitory Signals: Tumor Suppressor Genes TP53: Guardian of the Genome  Patients with the rare Li-Fraumeni syndrome inherit one defective copy of TP53 in the germ line, such that only one additional mutation is required to lose normal p53 function. Li-Fraumeni syndrome patients are prone to develop a wide variety of tumors.  As with RB, p53 can be incapacitated when bound by proteins encoded by oncogenic DNA viruses such as HPV. Mechanism and Causes of Neoplasia  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Insensitivity to Growth Inhibitory Signals: Tumor Suppressor Genes TGF-β, Contact Inhibition, and APB-β Catenin Pathways  TGF-β inhibits proliferation of many cell types by activation of growth-inhibiting genes such as CDKIs and suppression of growth-promoting genes such as MYC and those encoding cyclins.  Compromised in many tumors by mutations in its receptors (colon, stomach, endometrium) or by mutational inactivation of SMAD genes that transduce TGF-β signaling (pancreas).  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Insensitivity to Growth Inhibitory Signals: Tumor Suppressor Genes TGF-β, Contact Inhibition, and APC-β Catenin Pathways  E-cadherin maintains contact inhibition, which is lost in malignant cells.  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Insensitivity to Growth Inhibitory Signals: Tumor Suppressor Genes TGF-β, Contact Inhibition, and APC-β Catenin Pathways  The APC gene exerts anti-proliferative actions by regulating the destruction of the cytoplasmic protein β- catenin.  With a loss of APC, β-catenin is not destroyed, and it translocates to the nucleus, where it acts as a growth- promoting transcription factor.  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Altered Cellular Metabolism  Even in the presence of ample oxygen, cancer cells demonstrate a distinctive form of cellular metabolism characterized by high levels of glucose uptake and increased conversion of glucose to lactose (fermentation) via glycolytic pathway.  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Evasion of Cell Death  Evasion of cell death by cancers mainly involved acquired abnormalities that interfere with the intrinsic (mitochondria) pathway of apoptosis.  The most common abnormalities involve loss of p53 function, either by way of TP53 mutations or overexpression of the p53 inhibitor MDM2.  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Evasion of Cell Death  Other cancers evade cell death by overexpressing anti- apoptotic members of the BCL2 family, such as BCL2, BCL-XL and MCL1, which protect cells from the action of BAX and BAK, the pro-apoptotic members of the BCL2 family.  BH-3 (BAD, BID, PUMA)  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Evasion of Cell Death  In a large majority of follicular B-cell lymphomas, BCL2 levels are high because of a (14; 18) translocation that fuses the BCL2 gene with regulatory elements of the immunoglobulin heavy chain gene.  Inhibitors of MDM2 (which activate p53) and inhibitors of BCL2 family members induce the death of cancer cells by stimulating the intrinsic pathway of apoptosis and are being developed as therapeutic agents.  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Limitless Replicative Potential (Immortality)  Tumor cells, unlike normal cells, are capable of limitless replication.  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Sustained Angiogenesis  Even if a solid tumor possesses all of the genetic aberrations that are required for malignant transformation, it cannot enlarge beyond 1 to 2 mm in diameter unless it has the capacity to induce angiogenesis.  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Sustained Angiogenesis  Vascularization of tumors is essential for their growth and is controlled by the balanced between angiogenic and anti-angiogenic factors that are produced by tumor and stromal cells.  Hypoxia triggers angiogenesis through the action of HIF- 1α on the transcription of the proangiogenic factor VEGF.  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Sustained Angiogenesis  Many other factors regulate angiogenesis; for example p53 induces synthesis of the angiogenesis inhibitor thrombospondin-1. Represses expression of VEGF  While RAS, MYC, and MAPK signaling all upregulate VEGF expression and stimulate angiogenesis.  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Sustained Angiogenesis  VEGF inhibitors are used to treat a number of advanced cancers and prolong the clinical course, but are not curative.  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Invasion and Metastasis  Ability to invade tissues, a hallmark of malignancy, occurs in 4 steps :  Loosening of cell-cell contacts,  Degradation of ECM,  Attachment to novel ECM components  Migration of tumor cells.  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Invasion and Metastasis  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Invasion and Metastasis  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Invasion and Metastasis  Cell-cell contacts are lost by the inactivation of E- cadherin through a variety of pathways.  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Invasion and Metastasis  Basement membrane and interstitial matrix degradation is mediated by proteolytic enzymes secreted by tumor cells and stromal cells, such as MMPs and cathepsins.  Proteolytic enzymes also release growth factors sequestered in the ECM and generate chemotactic and angiogenic fragments from cleavage of ECM glycoproteins.  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Invasion and Metastasis  The metastatic site of many tumors can be predicted by the location of the primary tumor.  Many tumors arrest in the first capillary bed they encounter (lung and liver, most commonly).  Some tumors show organ tropism, probably due to activation of adhesion or chemokine receptors whose ligands are expressed by endothelial cells at the metastatic site. Mechanism and Causes of Neoplasia  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Evasion of Immune Surveillance  Tumor cells can be recognized by the immune system as non-self and destroyed.  Genomic instability as an enabler of malignancy  Individuals with inherited mutations of genes involved in DNA repair systems are greatly increased risk for the development of cancer.  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Evasion of Immune Surveillance  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Evasion of Immune Surveillance  Mechanism and Causes of Neoplasia Hallmarks of Cancer: Tumor-Promoting Inflammation as an Enabler of Malignancy  Mechanism and Causes of Neoplasia Etiology of Cancer : Carcinogenic Agents  Carcinogenic agents inflict genetic damage  Mechanism and Causes of Neoplasia Etiology of Cancer : Carcinogenic Agents  Chemical Carcinogens  Chemical carcinogens have highly reactive electrophile groups that directly damage DNA.  Mechanism and Causes of Neoplasia Etiology of Cancer : Carcinogenic Agents  Chemical Carcinogens  Mechanism and Causes of Neoplasia Etiology of Cancer : Carcinogenic Agents  Chemical Carcinogens  Mechanism and Causes of Neoplasia Etiology of Cancer : Carcinogenic Agents  Chemical Carcinogens  Mechanism and Causes of Neoplasia Etiology of Cancer : Carcinogenic Agents  Chemical Carcinogens  Mechanism and Causes of Neoplasia Etiology of Cancer : Carcinogenic Agents  Radiation Carcinogenesis  Radiation, whatever its source (UV rays of sunlight, radiographs, nuclear fission, radionuclides), is an established carcinogen. Mechanism and Causes of Neoplasia  Mechanism and Causes of Neoplasia Etiology of Cancer : Carcinogenic Agents  Radiation Carcinogenesis  Ionizing radiation causes chromosome breakage, chromosome rearrangements and less frequently point mutations, any of which may affect cancer genes and thereby drive carcinogenesis. Mechanism and Causes of Neoplasia  Mechanism and Causes of Neoplasia Etiology of Cancer : Carcinogenic Agents  Radiation Carcinogenesis  UV rays in sunlight induce the formation of pyrimidine dimers within DNA, leading to mutations that can give rise to squamous cell carcinomas and melanomas of the skin.  Mechanism and Causes of Neoplasia Etiology of Cancer : Carcinogenic Agents  Viral and Microbial Oncogenesis o Oncogenic RNA Viruses o Oncogenic DNA Viruses o Hepatitis B and C Viruses o Helicobacter pylori  Mechanism and Causes of Neoplasia Etiology of Cancer : Carcinogenic Agents  Viral and Microbial Oncogenesis o Oncogenic RNA Viruses HTLV-1 causes a T cell leukemia that is endemic in Japan and the Caribbean. The HTL-1 genome encodes a viral protein called Tax, which stimulates proliferation, enhances cell survival, and interferes with cell cycle control.  Mechanism and Causes of Neoplasia Etiology of Cancer : Carcinogenic Agents  Viral and Microbial Oncogenesis o Oncogenic DNA Viruses o Human Papillomavirus o Epstein-Barr Virus  Mechanism and Causes of Neoplasia Etiology of Cancer : Carcinogenic Agents  Viral and Microbial Oncogenesis Human Papillomavirus HPV is associated with benign warts, as well as cervical cancer. Mechanism and Causes of Neoplasia  Mechanism and Causes of Neoplasia Etiology of Cancer : Carcinogenic Agents  Viral and Microbial Oncogenesis Human Papillomavirus The oncogenicity of HPV is related to the expression of two viral oncoproteins, E6 and E7, which bind to the p53 and RB tumor suppressors, respectively , neutralizing their function. E6 and E7 from high-risk strains of HPV (which give rise to cancers) have higher affinity for their targets than do E6 and E7 from low-risk strains of HPV (which give rise to benign warts).  Mechanism and Causes of Neoplasia Etiology of Cancer : Carcinogenic Agents  Viral and Microbial Oncogenesis CAP calls for the scrapping of the National HPV Vaccination Programme for 13- year-old Malaysian girls because it is irrelevant and the vaccines have deadly side- effects. The RM150 million project which targets 300,000 schoolgirls uses vaccines which protect against 4 HPV (Human Papillomavirus) types which had correlation with cervical cancer. There are about 200 HPV types in total — 40 of which are oncogenic. The vaccines are irrelevant because they ONLY protect against 2 to 4 out of more than 40 cancer-correlated HPV types. Gardasil protects against 4 HPV types and Cervarix protects against 2 HPV types. They do not protect against more than 36 other cancer-correlated HPV types.  Mechanism and Causes of Neoplasia Etiology of Cancer : Carcinogenic Agents  Viral and Microbial Oncogenesis  Mechanism and Causes of Neoplasia Etiology of Cancer : Carcinogenic Agents  Viral and Microbial Oncogenesis Epstein-Barr Virus EBV is implicated in the pathogenesis of Burkitt lymphomas, lymphomas in immunosuppressed patients, Hodgkin lymphoma, uncommon T-cell and NK-cell tumors, NPC, a subset of gastric carcinoma and rarely sarcoma.  Mechanism and Causes of Neoplasia Etiology of Cancer : Carcinogenic Agents  Viral and Microbial Oncogenesis Certain EBV gene products contribute to oncogenesis by stimulating normal B-cell proliferation pathways. Concomitant compromise of immune competence allows sustained B-cell proliferation, leading eventually to development of lymphoma.  Mechanism and Causes of Neoplasia Etiology of Cancer : Carcinogenic Agents  Viral and Microbial Oncogenesis o Hepatitis B and Hepatitis C Viruses 70-85% of hepatocellular carcinomas worldwide are due to infection with HBV or HCV The oncogenic effects of HBV and HCV are multifactorial but the dominant effect seems to be immunologically mediated chronic inflammation, with hepatocellular injury, stimulation of hepatocyte proliferation, and production of reactive oxygen species that can damage DNA. The HBx protein of HBV and HCV core protein can activate a variety of signal transduction pathways that also may contribute to carcinogenesis.  Mechanism and Causes of Neoplasia Etiology of Cancer : Carcinogenic Agents  Viral and Microbial Oncogenesis o Helicobacter pylori H. pylori infection has been implicated in both gastric adenocarcinoma and MALT lymphoma The mechanism of H. pylori-induced gastric cancers is multifactorial, including immunologically mediated chronic inflammation, stimulation of gastric cell proliferation, and production of reactive oxygen species that damage DNA. H. pylori pathogenicity genes, such as CagA, also may contribute by stimulating growth factor pathways.  Biological & Clinical Effects of Neoplasia Grading and Staging of Cancer: Biological & Clinical Effects of Neoplasia  Biological & Clinical Effects of Neoplasia Laboratory Diagnosis of Cancer  Morphologic Methods  Tumor Markers  Molecular Diagnosis  Molecular Profiling of Tumors: The future of Cancer Diagnostics  Biological & Clinical Effects of Neoplasia Laboratory Diagnosis of Cancer  Several sampling method approaches exist for the diagnosis of tumors, including excision, biopsy, fine needle aspiration, and cytologic smears  Biological & Clinical Effects of Neoplasia Laboratory Diagnosis of Cancer  Immunohistochemistry and flow cytometry studies help in the diagnosis and classification of tumors, because distinct protein expression patterns define different entities.  Biological & Clinical Effects of Neoplasia Laboratory Diagnosis of Cancer  Immunohistochemistry  Biological & Clinical Effects of Neoplasia Laboratory Diagnosis of Cancer  Proteins released by tumors into the serum, such as PSA, can be used to screen populations for cancer and to monitor for recurrence after treatment.  Biological & Clinical Effects of Neoplasia Laboratory Diagnosis of Cancer  Molecular analyses are used to determine diagnosis and prognosis, to detect minimal residual disease, and to diagnose patients with a hereditary predisposition to cancer.  Biological & Clinical Effects of Neoplasia Laboratory Diagnosis of Cancer  Molecular profiling of tumors by RNA expression profiling, DNA sequencing, and DNA copy number arrays are useful in molecular stratification of otherwise identical tumors or those of distinct histogenesis that share a mutation for the purpose of targeted treatment and prognostication.  Biological & Clinical Effects of Neoplasia Laboratory Diagnosis of Cancer  Assay of circulating tumor cells and of DNA shed into blood, stool, sputum, and urine are under development. Biological & Clinical Effects of Neoplasia Biological & Clinical Effects of Neoplasia Biological & Clinical Effects of Neoplasia Biological & Clinical Effects of Neoplasia