6. CHORISTOMA – have normal tissue, but not in normal place (ie.

NEOPLASIA I endometriosis)
Nomenclature – For Benign • heterotopic rest of normal tissue
Introduction Characteristics BENIGN MALIGNANT
•
nd st
2 leading cause of death in the US (1 = CVD) 1. MESENCHYMAL – organs lined with mesothelium
• Decreased mortality in the last decade of the 20th century and • Attach the suffix “oma” to the cell of origin
– Osteoma - bone Differentiation and Well differentiated Well to poorly/
in a downward course anaplasia undifferentiated/
– Chondroma - cartilagenous
– Fibroma – fibrous tissue anaplastic
Nomenclature Rate of growth Indolent/slow Rapid, erratic pace
*Neoplasma = tumor – Lipoma lipid tissue (not fat/ adipose)
growing/expansile-
• Neoplasia - new growth capsule
• Tumor - swelling 2. EPITHELIAL
• Oncology – study of tumors or neoplasms • Attach the suffix “oma” to the cell of origin, microscopic
pattern or macroscopic architecture Local invasion Absent Present-progressive
NEOPLASM infiltration/destruction
– Adenoma – glandular; forming glands
• Abnormal mass of tissue of
• Growth exceeds and uncoordinated with that of the normal – Papillomas – finger-like projections
– Polyp – protrudes from the surface of the organs surrounding/adjacent
tissue tissue
• Persists in the same manner after the cessation of stimuli – Cystadenomas, papillary cystadenomas
• Exception: Hepatoma, Lymphoma, Seminoma, Melanoma,
which evoked the change Metastasis Absent Present
Mesothelioma-malignant (found in pleura)
• Autonomous
• Clonal-arise from single cell that incurred genetic damage *all “-oma” are malignant
BENIGN Nomenclature – Malignant
1. CARCINOMA-from epithelial Differentiation & Anaplasia
• Relatively innocent
• Adenocarcinoma DIFFERENTIATION
• Remain localized
• Squamous cell carcinoma, basal cell carcinoma • Extent to which neoplastic parenchymal cells resemble the
• Cannot spread to other sites
corresponding normal parenchymal cells both
• Amenable to surgical removal
2. SARCOMA-from mesenchymal morphologically and functionally
• Patient generally survives
• liposarcoma, leiomyosarcoma, osteosarcoma ANAPLASIA – poorly differentiated
MALIGNANT
• fibrosarcoma, chondrosarcoma, angiosarcoma, • lack/loss of differentiation, associated with other morphologic
• Cancer
rhabdomyosarcoma changes
• Invade and destroy adjacent structures
• Spread to distant sites
• Cause death 3. MIXED TUMOR Changes in Anaplasia
• Divergent differentiation of a single neoplastic clone 1. PLEOMORPHISM – hallmark ok neoplasia
2 BASIC COMPONENTS • Pleomorphic adenoma of salivary gland (parotid) • Variation in size and shape – ex.big/small cells
2. ABNORMAL NUCLEAR MORPHOLOGY
1. parenchyma-clonal neoplastic cells
4. TERATOMA – from testis, embryo, ovarian • increased N:C ratio (1:6è1:1)
• determines tumor’s behavior and pathologic
• totipotential cell that differentiate along 3 germ cell layer – • hyperchromatic, large nucleoli
consequences
totipotent means it can make a whole body/anything 3. MITOSES – mitosis is normale in labile cells
2. stroma  supporting tissues; tells how fast will grow
• benign (mature) or malignant (immature) • increased, atypical, bizarre
• growth & evolution-blood supply
4. LOSS OF POLARITY
• connective tissue-framework
5. HAMARTOMAS – not necessary a neoplasia, it does not grow bigger • disturbed orientation
– Scant-soft and fleshy ex. Lymphoma,
Fibrosarcoma • disorganized but benign appearing masses composed of 5. TUMOR GIANT CELLS – NOT macrophages (ie. Langhan cells in
mature specialized cells or tissue indigenous to the particular TB)
– Abundant-desmoplasia (excessive stroma),
site • Not macrophages
stony hard ex. Scirrhous CA of breast
• pulmonary chondroid hamartoma, hemangioma 6. DYSPLASIA – if severe dysplasia, it is already equal in
carcinoma in situ (lesions confined in basement/noninvasive)
• loss in uniformity & architectural orientation of the cells

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 •disordered growth, often occurs in metaplastic – More aggressive, more rapidly growing, larger size- – Women: significant decline in death rates from
epithelium greater likelihood of metastasis cancer of breast & colorectal CA & most notably
7. METASTASIS – Approximately 30% of newly diagnosed individuals cervix-earlier diagnosis –Pap smear
• tumor implants discontinuous with the primary tumor with solid tumors present with metastasis – Men: nearly 80% of the total decrease in lung,
Rate of Growth – something to do w/stroma, needs blood supply prostate & colorectal CA
1. Doubling time of tumor cells – multiplication time remains the
same (3) Pathways of Spread
– Cell cycle time not shortened – time it takes to • Seeding of body cavities & surfaces
divide – Carcinomas arising from the ovaries Pseudomyxoma Geographic & Environmental Factors
2. Fraction of tumor cell in the replicative pool peritonei, appendiceal CA • Environmental > hereditary
– Growth fraction – affects the G0 (ie. Stable cells) • Lymphatics – carcinoma • Cultural > racial
• low in breast & colon, high in some – Skip metastasis – coz’ the passageway is obstructed • Environmental factors
leukemia, lymphoma & small cell CA – Sentinal nodes – Home - Outdoors
• Correlate with level of differentiation • Hematogenous – sarcoma – most common route – Work - Medication
• Hormonal stimulation, adequacy of blood – Veins>arteries *Look at table 7-3
supply, etc – Organ area for metastasis (liver & lung) = need to • Most overweight individuals have a higher death rate from CA
3. Rate at which cells are shed or die check fist • Alcohol abuse-increase the risk for oropharynx, larynx,
• Transplantation – rare esophagus, liver
CANCER STEM CELLS & CANCER CELL LINEAGES – If undergo surgery = it will spread because same • Smoking-mouth, pharynx, larynx, esophagus, pancreas,
• Cancer could arise from scalpel is used in making cuts bladder, kidney
– normal tissue stem cells or • Risk of cervical CA: age of first intercourse, number of sex
– More differentiated cells that acquire the property Epidemiology partners-HPV
of self-renewal • Study of cancer patterns
• CML- from stem cells • Contributes substantially to knowledge about origins of Age
• AML- differentiated myeloid precursors cancer • Most CA occur in later years of life >55yrs
• Tumor initiating cells (T-ICs) • Provides major insights on the cause of cancer • Main cause of death among women aged 40-79 and men
– Allow cells to grow indefinitely – environmental, racial (hereditary) & cultural aged 60-79 ….carcinomas
– May represent 25% of the total cellularity influences • Acute leukemia & neoplasm of the CNS-approx 60% of deaths
• Cancer incidence in children
Local Invasion Male Female • Common neoplasms of infancy & childhood-small round blue
• Most benign tumors develop a rim of compressed connective – 1. Prostate 1. Breast cell tumors, which includes:
tissue called a capsule – this are normal tissue that are – 2. Lung 2. Lung – Neuroblastoma, Wilms tumor, retinoblastoma,
pushed outside the lining forming capsule – 3. Colon 3. Colon acute leukemias, & rhabdomyosarcomas
• Cancers show infiltration, invasion and destruction of – 4. Bladder 4. Uterus
• Death - most people die w/lung ca
surrounding tissue Genetic Predisposition
– Invasiveness Male Female
1. Autosomal Dominant Inherited Cancer Syndromes
• most reliable feature that differentiates – 1. Lung (31%) 1. Lung (26%)
2. Defective DNA Repair Syndromes
benign from malignant tumor next to – 2. Prostate (10%) 2. Breast (15%)
3. Familial Cancers
development of metastasis – 3. Colon (8%) 3. Colon (9%)
– 4. Pancreas (5%) 4. Pancreas & Ovary (6%)
1. Autosomal Dominant Cancer Syndromes
Metastasis • Inheritance of single autosomal dominant mutant gene
• Unequivocally marks a tumor malignant Cancer Incidence greatly increases the risk of developing a tumor
• With few exceptions, all malignant tumors can metastasize • Increased death rate • Usually a point mutation in single allele of tumor suppressor
– Gliomas of CNS, basal cell carinoma of skin-locally – HCC (hepatocellular ca)-caused by HCV (hepa C) gene (RB)
invasive but rarely metastasize • Decreased death rate • Defect in the second allele occurs in somatic cells as a
consequence of chromosome deletion or recombination

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1. Carriers of mutant RB tumor suppressor gene have 10,000
folds increased risk-bilateral retinoblastoma
– Increased risk of developing second cancer, osteogenic
sarcoma
2. Familial adenomatous polyposis-inherit AD mutation of APC
tumor suppressor gene (APC0adenomatous polycystic
carcinoma)
– innumerable adenomas in colon, virtually 100% fated to
develop CA
3. Li-Fraumeni syndrome-germ line mutation in p53 gene
4. Multiple Endocrine Neoplasia (MEN) 1 & 2 mutation in menin
and RET tyrosine kinase
5. Hereditary Nonpolyposis colon cancer (HNPCC)-inactivation of
mismatch repair gene (HNPCC is both AD&AR)
Inherited Cancer Syndromes
GENERAL CHARACTERISTICS
• Tumors tend to arise in specific sites and tissues
– Except Li Fraumeni
• Associated with a specific marker phenotype
– Lisch nodule & café-au-lait spots
2. Defective DNA Repair Syndromes
• Generally autosomal recessive
• Defects in DNA repair  can cause DNA instability
• Xeroderma pigmentosum, Ataxia telagiectasia, Bloom
syndrome
• ★HNPCC – AD w/DNA repair defect
– colon CA, small int., endometrium, ovary
– most common cancer predisposition syndrome
3. Familial Cancers
• Breast, ovary, pancreas, …..colon, brain, melanomas,
lymphomas
• Characteristic features
– early age at onset - AR
– tumors arising in 2 or more close relatives
– Multiple or bilateral tumors
• Transmission pattern of familial cancers is not clear
Interactions Genetic & Nongenetic Factors
• Complex
• Genotype can significantly influence the likelihood of
developing environmentally induced cancers
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• Inherited variations (polymorphisms) of enzymes that – Genes involved in DNA repair
metabolize procarcinogens to their active carcinogenic forms 4. Haploinsufficiency-loss of gene function caused by damage to
can influence the susceptibility to cancer a single allele
– cytochrome P-450 enzymes – Single cell is palpak but the other one is normal. A
total of 2 alelles
5. Carcinogenesis is a multistep process at both the phenotypic
& genetic levels, resulting from the accumulation of multiple
mutations
– Tumor progression
Nonhereditary Predisposing Conditions
CHRONIC INFLAMMATION –can lead to neoplastic
• ex. Ulcerative colitis, Crohn disease, H. pylori gastritis, viral
hepatitis, chronic pancreatitis
• it is d/t Cytokines stimulate growth of transformed cells – that
stimulate jak stat receptors
• Increase pool of tissue stem cells
• Production of Reactive Oxygen Species
• Evidence: COX-2 increased in colon CA
PRECANCEROUS CONDITIONS
7 FUNDAMENTAL CHANGES
• non-neoplastic disorders
– chronic atrophic gastritis of pernicious anemia, solar 1. Self-sufficiency in growth factors
keratosis, skin chronic ulcerative colitis, & 2. Insensitivity to growth inhibitory signals
leukoplakia of oral vulva, penis & oral cavity 3. Evasion of apoptosis
• Neoplasic 4. Defects in DNA repair
– Villous adenoma-increase in size, develops CA in 5. Limitless replicative potential
50% of cases 6. Sustained angiogenesis
7. Ability to invade and metastasize
Molecular Basis of Cancer
FUNDAMENTAL PRINCIPLES
1. Nonlethal genetic damage lies in the heart of carcinogenesis
– mutation may be acquired-action of environmental
agents: chemicals, radiation, viruses
– inherited in the germ line
– if cells died, there will be no replication & thus, it
must not be lethal
2. Tumor is formed by the clonal expansion of single precursor
cell that has incurred the genetic damage
– Tumors are monoclonal
– Cells that gone crazy
3. Four classes of normal regulatory genes are the principal
target of genetic damage
– Protooncogenes-growth promoting
– Tumor suppressor gene-growth inhibiting
– Genes that regulate apoptosis
SELF SUFFICIENCY IN GROWTH SIGNALS – kinase is transiently activated by binding of the • Can act in concert to reprogram somatic cells into
• ONCOGENES - Genes that promote autonomous growth specific GF, followed rapidly by receptor pluripotent stem cells
• PROTONCOGENES - Normal cellular counterpart dimerization & tyrosine phosphorylation of several • May also enhance self-renewal, block differentiation or
• ONCOPROTEINS - Products of genes without regulatory substrate that are part of signaling cascade both
function • Oncogenic/mutant receptors • Amplified in breast, colon, lung and many other
*Proto-oncogenes  oncogene  secretes oncoproteins – associated with constitutive dimerization & carcinomas
activation without binding to the GF, deliver • N-MYC & L-MYC in neuroblastomas & small cell CA of
continuous mitogenic signals to the cell even in the lungs respectively
absence of GF in the environment • Translocation-Burkitts lymphoma
• Can be constitutively activated in tumors by different
STEPS IN CELL PROLIFERATION
mechanisms CYCLINS
• Binding of growth factor to cell membrane receptor – Mutations
• Activation of signal transducing proteins – gene rearrangements
• Transmission of signal to nucleus – overexpression
• Activation of nuclear factors Ex. RET proto-oncogene : mutation with gene rearrangement
• Entry into cell cycle – MEN-2A & MEN-2B
• Over expression of normal forms of GF receptors
– By gene amplification and other unknown
mechanisms
Ex. EGFR
• ERBB1-overexpressed in SCCA of the lung,
glioblastomas, head & neck tumors  Control orderly progression of cells thru the phases of the cell
cycle
Signal Transducing Proteins
CDK Inhibitors
• Oncoprotein can mimic signal transducing proteins
• CIP/WAF
• ex. RAS family of guanine triphosphate (GTP)-binding proteins
– p21,p27,p57
(G proteins)-RAS genes
– Inhibit all stages
• INK4
RAS Oncogene
– p15, p16, p18, p19
• Point mutation of RAS family genes-single most common
– Inhibit cyclin D
abnormality of protooncogene in human tumors-approx.
• CDK4 & CDK6
15-20% of all human tumors
• Check points at G1/S and G2/M mediated
• 90% in pancreatic adenoCA & cholangioCA
by p53, p21
• 50% in colon, endometrial, thyroid
Growth Factors • Major cause of genetic instability
• 30% in lung adenoCA & myeloid leukemia
• Normal cells • KRAS-colon & pancreas, HRAS-bladder, NRAS-
– need GF to stimulate proliferation SELF SUFFICIENCY OF GROWTH SIGNALS
hematopoeitic tumors
– paracrine action • Overexpression of growth factor genes
• Many cancer cells – PDGF & TGF
• Activated RAS stimulates downstream regulators of
– acquire the ability to synthesize the same GF to • Altered growth factor receptors
proliferation such as the mitogen-activated protein (MAP)
which they are responsive – RET
kinase cascade-floods the nucleus with signals for cell
– autocrine loop • Minicry of signal transducing proteins
proliferation
Ex. Glioblastoma-express PDGF &PDGFR – RAS
• Mutated RAs is trapped in its activated GTP-bound form, and
Sarcomas-TGFα • Oncoproteins as transcription factors
the cell is forced into continuously proliferating state
– MYC
Growth Factor Receptors • Dysregulation of cyclins
MYC Oncogene
• Normal

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INSENSITIVITY TO GROWTH INHIBITORY SIGNALS  PTCH- “Gorlin syndrome”, basal cell carcinoma
• TUMOR SUPPRESSORS
– Stop cell proliferation
• RB gene NEOPLASIA PART II
• P53 protein
• APC and NF-1
EVASION OF APOPTOSIS
• Reduced levels of CD95/Fas – inhibit extrinsic pathway
Knudson’s Hypothesis
• Inactivation of caspase 8 by FLIP – inhibit extrinsic path.
• “two hits” required
• Protection of tumor cells by BCL2
– First hit - inherited, all somatic cells
– Second hit- inherited or acquired, particular cell
• “loss of heterozygosity” LIMITLESS REPLICATIVE POTENTIAL
– Heterozygotes-no expression of cancer • Replicative senescence lies in telomere shortening
– Homozygotes-cancer • Short telomere  activation of p53 checkpoint  apoptosis
• Telomerase-prevents shortening of telomere
RB GENE • About 90% of tumors have telomerase activity
• RB protein regulates cell growth at G1/S • Some have alternative lengthening of telomeres
• Cyclin E- CDK2 and Cyclin D CDK 4,6 required
• Mutation associated with retinoblastoma and osteosarcoma SUSTAINED ANGIOGENESIS
• Loss of normal cell cycle control is central to malignant • Tumors >2mm require new blood supply
transformation and that at least 1 of 4 key regulators of the • Angiogenic switch- change in phenotype that induces
cell cycle is dysregulated in the vast majority of human APC/ CATENIN angiogenesis mostly controlled by hypoxia
cancers • APC protein down regulates catenin • Neovascularization (adult) or vasculogenesis – this 2 both
• Loss of APC causes continuous WNT signaling and -catenin occur in neoplasia
p53 (p63,p73) enters nucleus  cell proliferation • Vasculature is abnormal- leaky, haphazard
• Most common target for genetic alteration • Vasculogenic mimicry – tumor cells resemble capillaries
• Located on chromosome 17p13.1 • The only difference is that there is no blood inside
• Stops neoplastic transformation by Notes:
– Cell cycle arrest (quiescence and senescence) • Decreased angiogenesis inhibitors – angiostatin, endostatin,
– initiation of apoptosis vasculostatin
• One mutant p53 = Li Fraumeni syndrome • Loss of p53 provides more permissive environment for
– 25 % increased risk of neoplasia angiogenesis
– Sarcomas, breast, leukemia • Vegf expressed on tumor cells – culprit in angiogenesis
• Vasculogenic mimiccry no longer in book!

METASTATIC CASCADE
• Two phases
1. Invasion of the extracellular matrix
2. Vascular dissemination, homing of tumor cells and
colonization
TUMOR SUPPRESSORS
 NF1-Neurofibroma, glioma 1. INVASION
 NF2- Schwannoma • Detachment of tumor cells from one another
 VHL – renal cell ca, pheochromocytoma – Down regulation of E cadherins – becomes loose
 PTEN- “Cowden Syndrome” epithelial cancers • Degradation of ECM
 WTI- Wilms

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 – Secrete proteolytic enzymes: MMPs, cathepsin D, – Snail and twist promote EMT epithelial to mesenchymal – Loss of tumor suppressor genes
urokinase, plasminogen transition.which favors migration • Non hematopoietic solid tumors
• Attachment to matrix components • RB in retinoblastoma
– Intergrins attach to fibronectin, laminin Genomic Instability
• Migration of tumor cells or locomotion • Where DNA become vulnerable for mutations (irreversible) Gene Amplification
– Directed by cell derived cytokines/ amoeboid mov’t • Inherited defects in DNA repair genes allow mutations in • Two patterns are seen
other genes – double minutes (dms)
Notes: • DNA repair systems – Homogeneous Staining Regions (HSR)
• Down regulation of E catherins or mutation in catenin needed – Mismatch - can cause: – Ex. N-MYC – neuroblastoma, both patterns seen
for linkage • HHPCC – microsatellite instability – Ex. ERBB2 – breast ca
• Matrix metalloproteinases – remodelng insoluble components – Nucleotide excision repair
and release of growth factors • Xeroderma pigmentosa (AR) – sensitive to Epigenetic Changes
• Ameoboid migration- a second method of migration using uv light – Reversible, heritable changes in gene expression
collagen fibers – Recombination repair – Post translational modification
• Bloom, etc – hypersensitivity to DNA – Genome imprinting / loss of imprinting d/t
damaging agents – Methylation causes inactivation
• BRCA 1 &BRCA 2 breast cancer Ex BRCA 1 in breast cancer
Notes:
• Genonic instability occurs when both DNA repair genes are MiRNAs and Cancer
lost • Small non-coding single stranded RNA
• Microsatellite instability- tandems are shorter or longer • Mediate post-transcriptional gene silence
• UV radiation causes cross-linkage of pyrimidine residues that
now cannot be excised
Multistep Carcinogenesis
• Cancer must result from the accumulation of multiple
Warburg Effect – a metabolic alterations mutations
• Does not want yo breakdown glucose; inhibit kreb’s cycle
• Tumors shift to aerobic glycolysis
• Not on Oxygen-hunger  more onn Glucose hunger
• Possible explanation
– Increased need for energy of dividing cell
2. VASCULAR DISSEMINATION – Abnormal vasculature
• Tumor cells -clump, form emboli, adhere to target (emboli is – Reduction in autophagy
filled with platelet & metabolite) Notes:
• At site -proliferate, develop a vascular supply, evade host • Used to visualize tumors in PET
defenses • Gives 2 ATP rather than 20
• Organ trophism –
– Adhesion molecules on the endothelial cells of the
target organ
Chromosomal Abnormalities
– Chemokine receptors
– Translocation
– Some tissues are unfavorable to metastasis ( where
– Overexpression of protooncogenes
we do not see metastasis, ex.skeletal muscles)
• MYC of Burkitt Lymphoma
Notes: Carcinogenesis
– Hybrid “chimaric” genes
– Some tissues, like skeletal muscles have an unfavorable Initiation-promotion sequence
– Constitutive tyrosine kinase activity
environment for growth 1. Initiation results from exposure of cells to a sufficient dose of
• BCR-ABL (Philadelphia chromosome 9) of CML
– CD44 – are adhesion molecule expressed on T cells; carcinogen
• BCR( 22) to ABL (9)
overexpression favors metatasis – Permanent DNA damage is rapid and irreversible
– Deletions

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 2. Promoters induce tumors in initiated cell without affecting • Bile salts • HPV also activate cyclins, inhibit apoptosis and combat cell
DNA directly and are reversible • High levels of dietary fat aging
– Not tumorigenic themselves; only cause cell • phenols • EBV uses CD 21 receptor to attach to B cells
proliferation
2. RADIATION CARCINOGENS Tumor Immunity
CARCINOGENS • Ultra Violet rays • Immune surveillance
1. Chemical – UV B in sunlight linked to all forms of skin cancer – – Guards against tumor development
2. Radiant energy can cause squamous cell Ca - melanoma • Cancer immunoediting
3. Microbial – Formation of pyrimidine dimers – Sculpting the immunogenic properties of tumors to
• Ionizing Electromagnetic Forces select tumor cells that escape immune elimination
1. CHEMICAL CARCINOGENS – X rays and gamma rays
• Initiation –  and  particles Tumor Antigens
– Exposure and mutation – linked to leukemias, thyroid ca etc 1. Products of mutated genes
• Promotion – Mutated tumor suppressor genes
– Reversible enhancement of proliferation Notes: – Mutated self protein
• Accumulated even exposure (SCC), short bursts of Notes:
INITIATORS – cause damage; direct (alkalyting agent); or indirect exposure (melanoma) – Tumor specific or tumor associated antigen no
• Direct acting • UVC more carcinogenic but filtered by ozone longer used!!
– Highly reactive electrophils – Antigens must be recognized by CTLs
– Weak carcinogens 3. MICROBIAL CARCINOGENS – Products of mutated genes become tumor antigens
• Indirect acting 1. RNA viruses - HTLV-1
– Require metabolic activation – T –cell leukemia, lymphoma 2. Overexpressed or aberrantly expressed cellular proteins
– Vary among individuals – tax genone causes proliferation and instabiity – Ex – tyrosinase and cancer testis antigen
2. Bacteria - Helicobacter pylori – Normal cellular proteins that are abnormally
 DNA is primary target – Gastric adenocarcinomas and MALTomas expressed!
 Altered cells must be able to undergo at least one cycle so – CagA cytotoxin gene and cytokines (Chronic 3. Produced by Oncogenic viruses
change can be made permanent inflammation) 4. Oncofetal antigens found on fetal and cancer cells
CARCINOGENIC CHEMICALS 5. Altered cell surface glycolipids and glycoproteins
* Liver cancer caused by Aflatoxin B has a signature mutation in (p53) – Higher concentration
Alkylating agents Naturally occurring Notes: – Abnormal forms
Weak - direct acting Aflatoxin B • Tax has transforming activity 6. Cell type specific differentiation antigens
Therapeutic agents Stored corn, rice, peanuts • H pylori – 1st bacteria called a carcinogen – Do not induce immune response
– target for immunotherapy
Polycyclic hydrocarbons Nitrosamines and amides 3. DNA viruses
Most potent Preservatives – Human Papilloma Virus (16 & 18) Anti Tumor Mechanisms
Tobacco, smoked meat/fish • Squamous cell ca of cervix d/t
• Cytotoxic T lymphocytes – cell mediated
• Overexpression of E6 & E7 oncogenes
• Natural killer cells
Aromatic amines/Azo dyes Others: – Epstein – Barr Virus
• Macrophages
Mainly affect liver asbestos, vinyl chloride, arsenic • Burkitt lymphoma, B cell (coz’ CD21)
• Antibodies - humoral
Food coloring Industrial exposure, insecticides lymphoma in HIV, Hodgkin,
Notes:
Nasopharyngeal Ca, gastric Ca,NK
• Mostly cell mediated
lymphoma
• Antibody against CD20 for B cell lymphoma
PROMOTERS • LMP-1 is oncogene
• Phorbol esters – Hepatitis B & C Viruses
Tumor Evasion of the Immune System
• Viral infection • Liver Cancer
• Cytokines and reactive oxygen species • Selective outgrowth of antigen-negative variants
• Hormones
• Loss or reduced expression of MHC molecules
Notes:

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 • Lack of costimulation • Tumor antigen cross reaction "The stage is T-3, N-1, M-0" which means "the cancer has spread
• Immunosuppression – ex. HIV 7. Acanthosis Nigricans – hyperpigmentation of the skin through the stomach wall, there is some spread to local lymph nodes,
• Antigen masking but no metastases in other parts of the body".
• Apoptosis of cytotoxic T cells 8. Hypertrophic osteoarthropathy (from bronchogenic)
• *Cancers more common in immunocompromised – New bone formation Laboratory Diagnosis
– Arthritis 1. Histologic & cytologic methods
Clinical Features of Tumors – Clubbing – Biopsy, needle aspiration (FNAB) & cytologic smears
Effects of Tumors on the Host 9. Vascular and hematologic (PAP) – stain not only for cervix
• Location & impingement on adjacent structures • Migratory thrombophlebitis (pancreas, lung) 2. Immunohistochemistry
• Functional activity such as hormone synthesis • Thrombotic endocarditis (adenocarcinoma) – Categorization of undifferentaiated malignancies
• Bleeding & secondary infection-ulcerate to surface • DIC (leukemia, prostate) – Determination of site of origin (PSA)
• Initiation of acute symptoms-rupture or infarction – Detection of molecules that have prognostic or
• Cachexia – 10% body weight loss Grading and Staging therapeutic value (ERBB2/ HER2-neu)
• Grading-degree of differentiation of the tumor cells and the * Cannot see loss of polarity, invasion, in FNAB and PAP
Local and Hormonal Effects number of mitosis within the tumor
• Destruction of remaining tissue-pituitary adenoma- – Usually 4 grades 3. Flow cytometry – give 3D view
endocrinopathies ie hypofunction • Staging is based on size of primary lesion, extent of regional – Individual cell characteristics
• Obstruction & intussuception lymph nodes, & presence or absence of blood borne 4. Molecular diagnosis – FISH & PCR, to look for cancer genes
• Fatal hypoglycemia-Beta cell adenoma metastasis. – Diagnosis
• Hematuria-renal – 2 staging system: UICC (TNM) & AJCC – Prognosis
• Melena-GIT – Detection of residual disease
* Stage more clinically significant than grade – Hereditary disposition
Cancer Cachexia *spread & size is important
• Progressive loss of body fat & lean body mass
• Weakness, anorexia and anemia  T stands for tumour - how far the primary tumour has grown
• Increased basal metabolic rate locally.
• Action of soluble factors-cytokines-TNF, IL-1, IFN-gamma,  N stands for nodes - if the cancer has spread to the local
Leukemia Inhibitory Factor (LIF) lymph nodes.
 M stands for metastases - if the cancer has spread to other
parts of the body.
Paraneoplastic Syndromes
s/sx no connection with neoplastic T0 – carcinoma in situ; do not invade yet
1. May present the earliest manifestation of an occult neoplasm N0 – no lymph node involved Tumor Markers*
2. May represent significant clinical problems and may even be M0 – no metastasis • HCG
lethal – choriocarcinoma
3. May mimic metastatic disease and therefore confound Example: stomach cancer • AFP
treatment  T-1 means the primary tumour is still in the stomach wall. T-3 – HCC
means the primary tumour has grown right through the • CEA
4. Endocrinopathies stomach wall and T-4 means it is invading nearby structures – colon, pancreas
• Cushing syndrome (most common endocrine), such as the pancreas. • PSA, PAP
ectopic hormone production in lung – prostate
 N-0 means there is no spread to lymph nodes. N-1 means that
5. Hypercalcemia (most common paraneoplastic) • NSE
some local lymph nodes are affected. N-2 means more
• Osteolysis – SCCL and neuroblastoma
extensive spread to local lymph nodes.
• Calcemic humoral substances (PTHRP) • CA 125
• NOT due to skeletal metastasis  M-0 means there are no metastases. M-1 means that there – ovarian
6. Neuromyopathic syndromes are metastases to some other area of the body such as the • CA-19-9
liver or brain.

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 – colon, pancreas
• CA-15-3
– breast

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