2. NEOPLASIA (TUMORS)NEOPLASIA (TUMORS)
DefinitionsDefinitions
NomenclatureNomenclature
Biology of Tumor GrowthBiology of Tumor Growth
EpidemiologyEpidemiology
Molecular Basis of CancerMolecular Basis of Cancer
Molecular Basis of CarcinogenesisMolecular Basis of Carcinogenesis
Agents (The Usual Suspects)Agents (The Usual Suspects)
Host Defense (Tumor Immunity)Host Defense (Tumor Immunity)
Clinical Features of TumorsClinical Features of Tumors
3. Defnition of NeoplasiaDefnition of Neoplasia
“A neoplasm is an abnormal mass of tissue, the growth
of which exceeds and is uncoordinated with that of
the normal tissues and persists in the same excessive
manner after cessation of the stimuli which evoked
the change” - Willis
Genetic changes
Autonomous
Clonal
4. Nomenclature – Benign TumorsNomenclature – Benign Tumors
-oma = benign neoplasm-oma = benign neoplasm
Mesenchymal tumorsMesenchymal tumors
chrondroma: cartilaginous tumorchrondroma: cartilaginous tumor
fibroma: fibrous tumorfibroma: fibrous tumor
osteoma: bone tumorosteoma: bone tumor
Epithelial tumorEpithelial tumor
adenoma: tumor forming glandsadenoma: tumor forming glands
papilloma: tumor with finger like projectionspapilloma: tumor with finger like projections
papillary cystadenoma: papillary and cystic tumor formingpapillary cystadenoma: papillary and cystic tumor forming
glandsglands
polyp: a tumor that projects above a mucosal surfacepolyp: a tumor that projects above a mucosal surface
8. Nomenclature – Malignant TumorsNomenclature – Malignant Tumors
Sarcomas: mesenchymal tumorSarcomas: mesenchymal tumor
chrondrosarcoma: cartilaginous tumorchrondrosarcoma: cartilaginous tumor
fibrosarcoma: fibrous tumorfibrosarcoma: fibrous tumor
osteosarcoma: bone tumorosteosarcoma: bone tumor
Carcinomas: epithelial tumorsCarcinomas: epithelial tumors
adenocarcinoma: gland forming tumoradenocarcinoma: gland forming tumor
squamous cell carcinoma: squamous differentiationsquamous cell carcinoma: squamous differentiation
undifferentiated carcinoma: no differentiationundifferentiated carcinoma: no differentiation
note: carcinomas can arise from ectoderm,note: carcinomas can arise from ectoderm,
mesoderm, or endodermmesoderm, or endoderm
9.
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13.
14. Tumors with mixed differentiationTumors with mixed differentiation
mixed tumors: e.g. pleomorphic adenoma of salivary glandmixed tumors: e.g. pleomorphic adenoma of salivary gland
carcinosarcomacarcinosarcoma
TeratomaTeratoma
tumor comprised of cells from more than one germ layertumor comprised of cells from more than one germ layer
arise from totipotent cells (usually gonads)arise from totipotent cells (usually gonads)
benign cystic teratoma of ovary is the most commonbenign cystic teratoma of ovary is the most common
teratomateratoma
Aberrant differentiation (not true neoplasms)Aberrant differentiation (not true neoplasms)
Hamartoma: disorganized mass of tissue whose cell types areHamartoma: disorganized mass of tissue whose cell types are
indiginous to the site of the lesionindiginous to the site of the lesion
Choriostoma: ectopic focus of normal tissue (heterotopia)Choriostoma: ectopic focus of normal tissue (heterotopia)
MisnomersMisnomers
hepatoma: malignant liver tumorhepatoma: malignant liver tumor
melanoma: malignant skin tumormelanoma: malignant skin tumor
seminoma: malignant testicular tumorseminoma: malignant testicular tumor
lymphoma: malignant tumor of lymphocyteslymphoma: malignant tumor of lymphocytes
18. Natural History Of Malignant TumorsNatural History Of Malignant Tumors
1.1. Malignant change in the targetMalignant change in the target
cell, referred to ascell, referred to as
transformationtransformation
2.2. Growth of the transformed cellsGrowth of the transformed cells
3.3. Local invasionLocal invasion
4.4. Distant metastases.Distant metastases.
19. DifferentiationDifferentiation
Well differentiated neoplasmWell differentiated neoplasm
Resembles mature cells of tissue of originResembles mature cells of tissue of origin
Poorly diffentiated neoplasmPoorly diffentiated neoplasm
Composed of primitive cells with littleComposed of primitive cells with little
diffrerentiationdiffrerentiation
Undifferentiated or “anaplastic” tumorUndifferentiated or “anaplastic” tumor
Correlation with biologic behaviorCorrelation with biologic behavior
Benign tumors are well differentiatedBenign tumors are well differentiated
Poorly differentiated malignant tumors usuallyPoorly differentiated malignant tumors usually
have worse prognosishave worse prognosis
20. If cells LOOK BAD, they are probably going to BEHAVE BAD
21. If cells LOOK GOOD, they are probably going to BEHAVE GOOD
22.
23. PleomorphismPleomorphism
SizeSize
shapeshape
Abnormal nuclear morphologyAbnormal nuclear morphology
HyperchromasiaHyperchromasia
High nuclear cytoplasmic ratioHigh nuclear cytoplasmic ratio
Chromatin clumpingChromatin clumping
Prominent nucleoliProminent nucleoli
MitosesMitoses
Mitotic rateMitotic rate
Location of mitosesLocation of mitoses
Loss of polarityLoss of polarity
““ANAPLASIA”ANAPLASIA”
24.
25. DysplasiaDysplasia
Literally means abnormal growthLiterally means abnormal growth
Malignant transformation is a multistep processMalignant transformation is a multistep process
In dysplasia some but not all of the features ofIn dysplasia some but not all of the features of
malignancy are presentmalignancy are present
DysplasiaDysplasia maymay develop into malignancydevelop into malignancy
Uterine cervixUterine cervix
Colon polypsColon polyps
Graded as low-grade or high-gradeGraded as low-grade or high-grade
Dysplasia mayDysplasia may NOTNOT develop into malignancydevelop into malignancy
26.
27.
28. Tumor Growth RateTumor Growth Rate
Doubling time of tumor cellsDoubling time of tumor cells
Lengthens as tumor growsLengthens as tumor grows
30 doublings (1030 doublings (1099
cells) = 1 gcells) = 1 g (months to years)(months to years)
10 more doublings (1 kg) = lethal burden10 more doublings (1 kg) = lethal burden (“)(“)
Fraction of tumor cells in replicative poolFraction of tumor cells in replicative pool
May be only 20% even in rapidly growing tumorsMay be only 20% even in rapidly growing tumors
Tumor stem cellsTumor stem cells
Rate at which tumor cells are shed or lostRate at which tumor cells are shed or lost
ApoptosisApoptosis
MaturationMaturation
Implications for therapyImplications for therapy
31. Features of Malignant TumorsFeatures of Malignant Tumors
Cellular featuresCellular features
Local invasionLocal invasion
CapsuleCapsule
Basement membraneBasement membrane
MetastasisMetastasis
Unequivocal sign of malignancyUnequivocal sign of malignancy
Seeding of body cavitiesSeeding of body cavities
LymphaticLymphatic
HematogenousHematogenous
32.
33.
34.
35.
36.
37.
38.
39. Significance of Nodal MetsSignificance of Nodal Mets
Example of breast cancerExample of breast cancer
Halsted radical mastectomyHalsted radical mastectomy
Sentinel node biopsySentinel node biopsy
PrognosticPrognostic
Number of involved nodes is an importantNumber of involved nodes is an important
component of TNM staging systemcomponent of TNM staging system
TherapeuticTherapeutic
Overall risk of recurrenceOverall risk of recurrence
Extent of nodal involvementExtent of nodal involvement
Histologic grade and other considerationsHistologic grade and other considerations
““Adjuvant” chemotherapyAdjuvant” chemotherapy
40. Benign vs Malignant FeaturesBenign vs Malignant Features
FeatureFeature BenignBenign MalignantMalignant
Rate of growthRate of growth Progressive butProgressive but
slow. Mitosesslow. Mitoses
few and normalfew and normal
Variable. MitosesVariable. Mitoses
more frequentmore frequent
and may beand may be
abnormalabnormal
DifferentiationDifferentiation WellWell
differentiateddifferentiated
Some degree ofSome degree of
anaplasiaanaplasia
Local invasionLocal invasion Cohesive growth.Cohesive growth.
Capsule & BMCapsule & BM
not breachednot breached
Poorly cohesivePoorly cohesive
and infiltrative.and infiltrative.
MetastasisMetastasis AbsentAbsent May occurMay occur
41.
42.
43.
44.
45.
46. Geographic & EnvironmentalGeographic & Environmental
Sun exposureSun exposure
Melanomas 6x incidence New Zealand vs IcelandMelanomas 6x incidence New Zealand vs Iceland
Blacks have low incidence of melanomaBlacks have low incidence of melanoma
Smoking and alcohol abuseSmoking and alcohol abuse
Body massBody mass
Overweight = 50% increase in cancerOverweight = 50% increase in cancer
Environmental vs racial factorsEnvironmental vs racial factors
Japanese immigrants to USAJapanese immigrants to USA
Viral exposureViral exposure
Human papilloma virus (HPV) and cervical cancerHuman papilloma virus (HPV) and cervical cancer
Hepatitis B virus (HBV) and liver cancer (Africa)Hepatitis B virus (HBV) and liver cancer (Africa)
Epstein-Barr Virus (EBV) and lymphomaEpstein-Barr Virus (EBV) and lymphoma
47. Change In Incidence Of Various Cancers With
Migration From Japan To The United States
48. Predisposing Factors for CancerPredisposing Factors for Cancer
AgeAge
Most cancers occur in persons ≥ 55 yearsMost cancers occur in persons ≥ 55 years
Childhood cancersChildhood cancers
Leukemias & CNS neoplasmsLeukemias & CNS neoplasms
Bone tumorsBone tumors
Genetic predispostionGenetic predispostion
Familial cancer syndromesFamilial cancer syndromes
Early age at onsetEarly age at onset
Two or more primary relatives with the cancerTwo or more primary relatives with the cancer
Multiple or bilateral tumorsMultiple or bilateral tumors
Polymorphisms that metabolize procarcinogens, e.g., nitritesPolymorphisms that metabolize procarcinogens, e.g., nitrites
Nonhereditary predisposing conditionsNonhereditary predisposing conditions
Chronic inflammationChronic inflammation
Precancerous conditionsPrecancerous conditions
Chronic ulcerative colitisChronic ulcerative colitis
Atrophic gastritis of pernicious anemiaAtrophic gastritis of pernicious anemia
Leukoplakia of mucous membranesLeukoplakia of mucous membranes
49. MOLECULAR BASISMOLECULAR BASIS
of CANCERof CANCER
NON-lethalNON-lethal genetic damagegenetic damage
A tumor is formed by the clonal expansionA tumor is formed by the clonal expansion
of a single precursor cell (of a single precursor cell (monoclonalmonoclonal))
Four classesFour classes of normal regulatory genesof normal regulatory genes
PROTO-oncogenesPROTO-oncogenes
OncogenesOncogenes OncoproteinsOncoproteins
DNA repair genesDNA repair genes
Apoptosis genesApoptosis genes
Carcinogenesis is aCarcinogenesis is a multistepmultistep processprocess
50. TRANSFORMATION &TRANSFORMATION &
PROGRESSIONPROGRESSION
Self-sufficiency in growth signalsSelf-sufficiency in growth signals
Insensitivity to growth-inhibiting signalsInsensitivity to growth-inhibiting signals
Evasion of apoptosisEvasion of apoptosis
Defects in DNA repair: “Spell checker”Defects in DNA repair: “Spell checker”
Limitless replicative potential: TelomeraseLimitless replicative potential: Telomerase
AngiogenesisAngiogenesis
Invasive abilityInvasive ability
Metastatic abilityMetastatic ability
53. ONCOGENESONCOGENES
Are MUTATIONS of NORMAL genesAre MUTATIONS of NORMAL genes
(PROTO-oncogenes)(PROTO-oncogenes)
Growth FactorsGrowth Factors
Growth Factor ReceptorsGrowth Factor Receptors
Signal Transduction Proteins (RAS)Signal Transduction Proteins (RAS)
Nuclear Regulatory ProteinsNuclear Regulatory Proteins
Cell Cycle RegulatorsCell Cycle Regulators
Oncogenes code forOncogenes code for OncoproteinsOncoproteins
54. Category
PROTO-
Oncogene
Mode of
Activation
Associated Human
Tumor
GFs
PDGF-β chain SIS Overexpression Astrocytoma
Osteosarcoma
Fibroblast
growth factors
HST-1 Overexpression Stomach cancer
INT-2 Amplification Bladder cancer
Breast cancer
Melanoma
TGFα TGFα Overexpression Astrocytomas
Hepatocellular
carcinomas
HGF HGF Overexpression Thyroid cancer
55. Category
PROTO-
Oncogene
Mode of
Activation
Associated Human
Tumor
GF
Receptors
EGF-receptor
family
ERB-B1
(ECFR)
Overexpression Squamous cell carcinomas of
lung, gliomas
ERB-B2 Amplification Breast and ovarian cancers
CSF-1 receptor FMS Point mutation Leukemia
Receptor for
neurotrophic
factors
RET Point mutation Multiple endocrine neoplasia 2A
and B, familial medullary thyroid
carcinomas
PDGF receptor PDGF-R Overexpression Gliomas
Receptor for stem
cell (steel) factor
KIT Point mutation Gastrointestinal stromal tumors
and other soft tissue tumors
56. Category
PROTO-
Oncogene
Mode of
Activation
Associated Human
Tumor
Signal
Transduction
Proteins
GTP-binding K-RAS Point mutation Colon, lung, and pancreatic
tumors
H-RAS Point mutation Bladder and kidney tumors
N-RAS Point mutation Melanomas, hematologic
malignancies
Nonreceptor
tyrosine kinase
ABL Translocation Chronic myeloid leukemia
Acute lymphoblastic leukemia
RAS signal
transduction
BRAF Point mutation Melanomas
WNT signal
transduction
β-catenin Point mutation Hepatoblastomas,
hepatocellular carcinoma
57. Category
PROTO-
Oncogene
Mode of
Activation Associated Human
Tumor
Nuclear
Regulatory
Proteins
Transcrip.
activators
C-MYC Translocation Burkitt lymphoma
N-MYC Amplification Neuroblastoma,
small cell
carcinoma of lung
L-MYC Amplification Small cell
carcinoma of lung
58. MYCMYC
Encodes for transcription factorsEncodes for transcription factors
Also involved with apoptosisAlso involved with apoptosis
59. P53 and RASP53 and RAS
p53p53
Activates DNA repairActivates DNA repair
proteinsproteins
Sentinel of G1/SSentinel of G1/S
transitiontransition
Initiates apoptosisInitiates apoptosis
Mutated in more thanMutated in more than
50% of all human50% of all human
cancerscancers
RASRAS
H, N, K, etc., varietiesH, N, K, etc., varieties
Single most commonSingle most common
abnormality ofabnormality of
dominant oncogenes indominant oncogenes in
human tumorshuman tumors
Present in about 1/3 ofPresent in about 1/3 of
all human cancersall human cancers
63. DNA REPAIR GENE DEFECTSDNA REPAIR GENE DEFECTS
DNA repair is like a spell checkerDNA repair is like a spell checker
HNPCCHNPCC ((HHereditaryereditary NNon-on-PPolyposisolyposis CColonolon
CCancer): TGF-ancer): TGF-ββ,, ββ-catenin, BAX-catenin, BAX
Xeroderma Pigmentosum: UV fixing geneXeroderma Pigmentosum: UV fixing gene
Ataxia Telangiectasia: ATM geneAtaxia Telangiectasia: ATM gene
Bloom Syndrome: defective helicaseBloom Syndrome: defective helicase
Fanconi anemiaFanconi anemia
64. LIMITLESS REPLICATIVELIMITLESS REPLICATIVE
POTENTIALPOTENTIAL
TELOMERES determine the limitedTELOMERES determine the limited
number of duplications a cell willnumber of duplications a cell will
have, like a cat with nine lives.have, like a cat with nine lives.
TELOMERASETELOMERASE, present in >90% of, present in >90% of
human cancers, changes telomeres sohuman cancers, changes telomeres so
they will have UNLIMITEDthey will have UNLIMITED
replicative potentialreplicative potential
65. TUMOR ANGIOGENESISTUMOR ANGIOGENESIS
QQ: How close to a blood vessel must a cell be?: How close to a blood vessel must a cell be?
A: 1-2 mmA: 1-2 mm
Activation of VEGF and FGF-bActivation of VEGF and FGF-b
Tumor size is regulated (allowed) byTumor size is regulated (allowed) by
angiogenesis/anti-angiogenesis balanceangiogenesis/anti-angiogenesis balance
67. Invasion FactorsInvasion Factors
DetachmentDetachment ("loosening up") of("loosening up") of
the tumor cells from each otherthe tumor cells from each other
AttachmentAttachment to matrix componentsto matrix components
DegradationDegradation of ECM, e.g.,of ECM, e.g.,
collagenase, etc.collagenase, etc.
MigrationMigration of tumor cellsof tumor cells
70. CHROMOSOME CHANGES
in CANCER
TRANSLOCATIONS and INVERSIONS
Occur in MOST Lymphomas/Leukemias
Occur in MANY (and growing numbers) of
NON-hematologic malignancies also
72. Carcinogenesis is “MULTISTEP”
NO single oncogene causes cancer
BOTH several oncogenes AND several tumor
suppressor genes must be involved
Gatekeeper/Caretaker concept
Gatekeepers: ONCOGENES and TUMOR
SUPPRESSOR GENES
Caretakers: DNA REPAIR GENES
Tumor “PROGRESSION”
ANGIOGENESIS
HETEROGENEITY from original single cell
73. Carcinogenesis:
The USUAL (3) Suspects
Initiation/Promotion concept:
BOTH initiators AND promotors are needed
NEITHER can cause cancer by itself
INITIATORS (carcinogens) cause
MUTATIONS
PROMOTORS are NOT carcinogenic by
themselves, and MUST take effect AFTER
initiation, NOT before
PROMOTORS enhance the proliferation of
initiated cells
74.
75. Q: WHO are the usual suspects?
Inflammation?
Teratogenesis?
Immune
Suppression?
Neoplasia?
Mutations?
76. A: The SAME 3 that are
ALWAYS blamed!
1) ChemicalsChemicals
2) RadiationRadiation
3) InfectiousInfectious PathogensPathogens
77. CHEMICAL CARCINOGENS:
INITIATORS
DIRECT
β-Propiolactone
Dimethyl sulfate
Diepoxybutane
Anticancer drugs
(cyclophosphamide,
chlorambucil,
nitrosoureas, and others)
Acylating Agents
1-Acetyl-imidazole
Dimethylcarbamyl chloride
“PRO”CARCINOGENS
Polycyclic and Heterocyclic
Aromatic Hydrocarbons
Aromatic Amines, Amides,
Azo Dyes
Natural Plant and Microbial
Products
Aflatoxin B1 Hepatomas
Griseofulvin Antifungal
Cycasin from cycads
Safrole from sassafras
Betel nuts Oral SCC
79. CHEMICAL CARCINOGENS:
PROMOTORS
HORMONES
PHORBOL ESTERS (TPA), activate kinase C
PHENOLS
DRUGS
“Initiated” cells respond and proliferate
FASTER to promotors than normal cells
80. RADIATION CARCINOGENS
UV:UV: BCC, SCC, MM
IONIZING:IONIZING: photons and particulate
Hematopoetic and Thyroid (90%/15yrs) tumors
in fallout victims
Solid tumors either less susceptible or require a
longer latency period than LEUK/LYMPH
BCCs in Therapeutic Radiation
95. TUMOR MARKERS
HORMONES: (Paraneoplastic Syndromes)
“ONCO”FETAL: AFP, CEA
ISOENZYMES: PAP, NSE
PROTEINS: PSA, PSMA
GLYCOPROTEINS: CA-125, CA-19-5, CA-15-3
MOLECULAR: p53, RAS
NOTE: These SAME substances which can
be measured in the blood, also can be stained
by immunochemical methods in tissue
96. MICRO-ARRAYS
THOUSANDS of genes identified from
tumors give the cells their own identity
and FINGERPRINT and may give
important prognostic information as well
as guidelines for therapy. Some say this
may replace standard histopathologic
identifications of tumors.
What do you think?
Editor's Notes
Poorly differentiated carcinoma of breast.
Iowa Histopathology
Papillary adenoma of colon. Note the fingerlike projections of the tumor.
Iowa Histopathology
Figure 7-2 Colonic polyp.. Gross appearance of several colonic polyps.
Colonic polyp. This benign glandular tumor (adenoma) is projecting into the colonic lumen and is attached to the mucosa by a distinct stalk.
This view shows the transition from normal squamous epithelium into invasive carcinoma.
A hallmark of well differentiated squamous cell carcinoma is that the nests of invading cells still attempt to make keratin which then gets deposited in the center of the nests, resulting in a keratin "pearl".
From the Iowa Collection
Another characteristic of a well differentiated squamous cell carcinoma is that it still makes visible intercellular bridges.
Adenocarcinoma of color arising in a case of ulcerative colitis
Lymph node with undifferentiated large cell carcinoma of the lung. If these epithelial tumor cells formed little circular or tubular structures called “glands”, it might better be termed “adenocarcinoma”. If it showed any attempt at keratin formation, “pearls”, or intercellular bridges between tumor cells, it might best be termed “squamous cell” carcinoma.
From the Iowa collection
Figure 7-4 A, Gross appearance of an opened cystic teratoma of the ovary. Note the presence of hair, sebaceous material, and tooth. You do not need a microscope to appreciate this tumor produces both connective tissue as well as epithelial derived elements.
A microscopic view of a similar tumor shows sebaceous glands, respiratory epithelium, bone, and bone marrow.
Dermoid cyst of ovary (a component of benign cystic teratoma)
Iowa Collection
The strong relationship between histology and biologic behavior
The Mormon Tabernacle Choir
Leiomyoma of the uterus. This benign, well-differentiated tumor contains interlacing bundles of neoplastic smooth muscle cells that are virtually identical in appearance to normal smooth muscle cells in the myometrium.
Dysplasia means potential PRE-cancer. Anaplasia means cancer.
Anaplastic large cell carcinoma of lung showing cellular and nuclear variation in size and shape. No differentiation into squamous or glandular epithelium is evident. This is what we mean when we say, it looks “bad”, i.e., pleomorphic, hyperchromatic.
This epithelium shows severe dysplasia: Note that dysplastic basal cells characterized by cuboidal shape, high nuclear cytoplasmic ratio, hyperchromatism, mitotic activity, and some loss of orientation to the basement membrane, occupy the lower two thirds of the surface rather than just the basal row of cells. More differentiated cells which occupy the outer third, though still retaining some dysplastic nuclear features have the appearance of maturing squamous cells rather than basal cells, and eventually become flattened on the surface.
Carcinoma in situ: This section shows that the dysplastic basiloid cells go all the way to the surface and never undergo significant differentistion towards more differentiated flattened squamous cells. Note however that the basement membrane is still intact.
Figure 7-12 Biology of tumor growth. The left panel depicts minimal estimates of tumor cell doublings that precede the formation of a clinically detectable tumor mass. It is evident that by the time a solid tumor is detected, it has already completed a major portion of its life cycle as measured by cell doublings. The right panel illustrates clonal evolution of tumors and generation of tumor cell heterogeneity. New subclones arise from the descendants of the original transformed cell, and with progressive growth the tumor mass becomes enriched for those variants that are more adept at evading host defenses and are likely to be more aggressive. (Adapted from Tannock IF: Biology of tumor growth. Hosp Pract 18:81, 1983.)
Figure 7-13 Schematic representation of tumor growth. As the cell population expands, a progressively higher percentage of tumor cells leaves the replicative pool by reversion to G0, differentiation, and death. Radiation and chemotherapy work on dividing cells, so the size of the non-proliferative pool is important.
Note the sharply demarcated border and a thin capsule in this neoplasm which is composed of both proliferating fibrous stroma (fibro) and glands (adenoma). The tumor is at the right and normal breast is at the left. As shown in this view the fibroadenoma, a benign tumor, is well circumscribed and has a fibrous capsule. This view shows the proliferation of benign appearing fibroblasts (arrows) (i.e. the "fibro" component), and several glands (the "adeno" component).
The invasiveness aspect of solid tumors is how “cancer” got its name, i.e., “crab”-like
Invasiveness (aka, “infiltration”) has BOTH gross as well as microscopic connotations
Adenocarcinoma of the breast. Note that the fibrous stroma of the beast is infiltrated by tumor cells arranged in nests with some gland formation. The dense fibrous stroma results in the tumor having a very firm consistency (schirrous carcinoma). Every pathologist could look at this image, and instantly know it was carcinoma.
Lymph node with metastatic adenocarcinoma. In this case only a few remnants of normal lymph node tissue are seen. Find them.
In fact, this could even be a PRIMARY with some lymphoid tissue reacting to it.
Adjuvant chemotherapy in breast cancer reduces the incidence of recurrence and metastasis, but is toxic. Such treatment is not advised when the risk of recurrence is very low. Grade and stage are important prognostic factors, but are being supplemented by newer biologic markers.
Figure 1 indicates the most common cancers expected to occur in men and women in 2005. Among men, cancers of the prostate, lung and bronchus, and colon and rectum account for more than 56% of all newly diagnosed cancers. Prostate cancer alone accounts for approximately 33% (232,090) of incident cases in men. Based on cases diagnosed between 1995 and 2000, about 90% of these estimated new cases of prostate cancer are expected to be diagnosed at local or regional stages, for which 5-year relative survival approaches 100%.
Notice that although there are FIVE bullets on this slide, it really is the THREE USUAL SUSPECTS, isn’t it?
Figure 7-25 The change in incidence of various cancers with migration from Japan to the United States provides evidence that the occurrence of cancers is related to components of the environment that differ in the two countries. The incidence of each kind of cancer is expressed as the ratio of the death rate in the population being considered to that in a hypothetical population of California whites with the same age distribution; the death rates for whites are thus defined as 1. The death rates among immigrants and immigrants' sons tend consistently toward California norms. (From Cairns J: The cancer problem. In Readings from Scientific American-Cancer Biology. New York, WH Freeman, 1986, p. 13.)
EPIDEMIOLOGY of cancer
A proto-oncogene is a normal gene that can become an oncogene due to mutations or increased expression. Proto-oncogenes code for proteins that help to regulate cell growth and differentiation.
The various aspects of “malignant tansformation”.
This is a BEAUTIFUL chart!
CDK’s (kinases) are enzymes which PHOSPHORILATE proteins in preparation for the next phase of the cycle.
G1SG2M is regulated by Cyclins DEAB, respectively, and CDKs 4221, respectively.
Signal transduction is a generic term which refers to any process by which a cell converts one kind of signal or stimulus into another.
Note, in every case, there is a NORMAL gene (proto-oncogene) MUTATED to become an ONCOGENE, ultimately resulting in the expression of as tumor.
Note, in every case, there is a NORMAL gene (proto-oncogene) MUTATED to become an ONCOGENE, ultimately resulting in the expression of as tumor.
Note, in every case, there is a NORMAL gene (proto-oncogene) MUTATED to become an ONCOGENE, ultimately resulting in the expression of as tumor.
Note, in every case, there is a NORMAL gene (proto-oncogene) MUTATED to become an ONCOGENE, ultimately resulting in the expression of as tumor.
Myc (cMyc) codes for a protein that binds to the DNA of other genes. When Myc is mutated, or overexpressed, the protein doesn't bind correctly, and often causes cancer.
These are the TWO other most important and widely studied genes in cancer.
A RAS protein
It would be a good idea to have a familiarity with these genes, recognizing that mutations of them result in cancers.
NOTE: Problems of GROWTH SUPPRESSION, result in GROWTH being UN-regulated.
Mutations of genes resulting in EVASION of APOPTOSIS would also be a factor in carcinogenesis, wouldn’t it?
Telomeres are a sequence of repetitive bases at the ends of linear chromosomes that prevent adjacent chromosomes from attaching to each other.
Think about this? If a telomere is interfered with, perhaps by telomerase, it LOSES its ability to limit mitoses!
Think about this too: A tumor could NEVER be more than 1-2 mm, if it did not have the ability to generate blood vessels to feed it? Right?
Another AWESOME diagram! Most important diagrammatic explanation of malignancy I have ever seen.
FOUR orderly steps of “INVASION” (aka, INFILTRATION, or INVASIVENESS)
It would be wise to remember that these THREE genes are often discussed in the ability of tumors to METASTASIZE.
They are metastatic SUPRESSOR genes. So once again, metastasis, like carcinogenesis, is a LOSS of regulation.
Many/Most leukemias/lymphomas have fairly predictable chromosome translocations.
The Initiation/Promotion concept is what we have always know about he cause of cancer. You need TWO things: 2) carcinogens and 2) proliferation
Direct carcinogens initiators cause mutations DIRECTLY.
“Pro”-carcinogens initiators are metabolized into substances which are more direct.
A glancing familiarity with all these compounds is a good thing to have.
As you might suspect, promotors are NOT carcinogenic by themselves, but often are agents of hyperplasia, e.g., steroid hormones.
ALL THREE common types of skin cancer are related to UV radiation.
The FIVE common viruses associated with cancers should also be in your recollection.
CYTOTOXIC CD8+ T-CELLS are the main eliminators of tumor cells
These words could not be seen in a real classroom, but they can be seen in a virtual one!
Which one of these two is more important?
The main question in grading is: HOW WELL do the tumor cells look like the NORMAL cells from which they arose?
If they look A LOT like “normal” cells, it is a LOW grade with a GOOD prognosis, but perhaps a TUFF diagnosis.
If they look NOT like “normal” cells, it is a HIGH grade with a BAD prognosis, but perhaps an EASY diagnosis.