2. NEOPLASM
Neoplasia – process of new growth
Neoplasm = new growth
Oncology means study of tumor
Cancer ---- common term of all malignant tumors.
3. DEFINITION
Willis, definition of neoplasm
A neoplasm is an abnormal mass of
tissue, the growth of which exceeds and is
uncoordinated with that of normal tissue
and persist in the same excessive manner
after cessation of the stimuli which evoke
the change.
4. WHY DOES A NEOPLASM OCCUR?
Due to “heritable genetic changes that are
passed down from the ‘changed’
(neoplastic) cell to the progeny of tumor
cells
The genetic change allows these group of
cells to have excessive & unregulated
proliferation that becomes almost
completely autonomous
5. TUMORS ARE MONOCLONAL
The entire population of cells within a tumor are one
single cell that has incurred genetic change, and
hence tumors are said to be “clonal”
Clone= a group of cells arising from one single cell
by asexual division and having the same structure
and function as that of the parent cell
6. THE 5 PS OF NEOPLASIA
A neoplasm is:
Persistent
Purposeless
Parasitic
Progressive
PROLIFERATION
7. TYPES OF NEOPLASMS
(TUMORS)
Benign tumors
They remain localized cannot spread to other
sites and are amenable to local surgical removal
and patient survives.
Malignant tumors
They invade and destroy adjacent structures and
spread to distant sites to cause death of patient.
8. NOMENCLATURE
Two basic components
Parenchyma (proliferating
neoplastic cell)
Stroma (connecting tissue and
blood vessels)
Some tumors (sarcoma) stroma is
scanty so neoplasm is soft and fleshy.
Desmoplasia – Abundant colagenous
stroma
Schirrhous – Stony hard scirrhous
9. THREE BASIC GROUPS OF TUMORS
I. Composed of one parenchymal cell type
II. Composed of more than one parenchymal cell
type arising from same germ layer .
III. Composed of more than one germ layer
arising from totipotential cells.
12. OTHER TERMS
Melanoma
Hepatoma
Seminoma
Chorsitoma
Ectopic rest of normal tissue e.g. rest of
adrenal cells under the kidney capsule.
Hamartoma
Mass of disorganised but mature
specialized cells or tissue
13.
Mixed tumor:- Divergent differentiation f a single
line of parenchymal cells into an other tissue. These
tumors arise from single germ layer. E.g. mixed
tumor of salivary gland (pleomorphic adenoma)
Teratoma :- Made up of variety parenchymal cell,
arise from more than one germ layer. These tumors
arise from totipotent cells
e.g. Ovarian cyst teratoma (dermoidcyst)
14.
15.
16. BIOLOGY OF TUMOR GROWTH
Four phases of malignant tumor
Malignant changing in the target cell ---Transformation.
Growth of transformed cells .
Local invasion.
Distant metastasis.
17. Differentiation
Resemblance of neoplastic cells with
normal cells , both morphologically and
functionally .
Anaplasia ( to form backward )
lack of differentiation.
18. MORPHOLOGICAL CHANGES OF
ANAPLASIA
Pleomorphism .
Abnormal nuclear morphology .
Increase mitotic figure
Atypical mitotic figure
Loss of polarity .
Disorganization of tumor cells
Tumor giant cells.
Hyperchromatic
Large nucleus and irregular
Nucleoli present
Mitosis .
Variation in shape & size
19. Dysplasia
Disorder growth .
Reverse change may occur.
Pleomorphism . Loss of orientation ,
hyperchromatic nuclei , increase mitotic
activity.
Mostly seen in epithelium .
Carcinoma in situ, displastic changes are
marked and involve the entire thickness of
epithelium but the lesion remain confined to
the normal tissue.
30. RATE OF GROWTH
Rate of growth of tumor is determined by three
main factor
Doubling time of tumor cell.
Fraction of tumor cells,
the proportion of cells with in the tumor
population that are in proliferative pool.
Rate at which cells are shed and last in the
growing lesion.
31.
During early phase of cell growth transforms
cells are in the proliferative pool.
During growth of tumor , tumor cells leave the
proliferative pool and goes nonproliferative pool
(shading, apoptosis, differentiated and reversion
to Go
Most cells within tumor remain in the G0 or G1
phase.
Leukemia,lymphoma , lung tumor high growth
fraction.
32.
Colon, breast low growth fraction.
Increased growth fraction tumor increase
susceptibility to cancer therapy, decrease growth
fraction decrease susceptibility to cancer therapy.
Other factors like hormone , adequate blood
supply and unknown influences may effect their
growth.
37. METASTASIS
Implantation of tumor cells from primary site to
distant site .
Three routes .
Seeding of body cavities.
Lymphatic spread
Common e.g. Ca breast.
Skip metastasis.
Venous
lymphatic anastomoses by inflammation .
Radiation.
Sentinel lymph node.
First
node in regional lymphatic system that received lymph
flow from primary tumor.
39. FACTORS RESPONSIBLE FOR TUMOR
Environmental factors
Virus
Radiation .
Chemical agents.
Cigarette smoking.
Chronic alcoholism.
Risk of cervical cancer increase with increase
number of sex partner
40. GENETIC FACTOR
Three categories
Autosomal dominant inherited cancer
syndrome.
Point mutation in a single allele of tumor
suppressor gene.
Childhood retinoblastoma are common .
Mutation of the RB tumor suppressor gene.
Other e.g. osteogenic sarcoma.
Familial adenomatous polyposis.
Multiple endocrine neoplasia type I and II
(MEN1and MEN2).
Defective DNA repair syndrome.
Autosomal recessive pattern of inheritance .
Xeroderma pigmentosum.
Ataxia telangectasia.
41.
Hereditary non-polypoid colon cancer (HNPCC)
Autosomal
dominant condition caused by inactivation of DNA
mismatch repair gene.
HNPCC sydrome produce cancer in the colon, small intestine,
endomatrium and ovaries.
FAMILIAL
Without clearly defined pattern of transmission.
Ca
colon , breast, ovary, brain and malinoma are common.
Onset - early age.
Tumor arise from two or more close relative.
Some time bilatral or multiple tumor.
42. NON-HEREDITARY PREDISPOSING
CONDITION
Chronic inflmmation and cancer
Ulcerative colitis , Crohn’s disease ,
helicobacter pylori gastritis , viral hepatitis,
chronic pancreatitis.
Unknown
cause but (1) may be release of certain
cytokinese which stimulate the growth of
transforms cells.
Chronic inflammation may directly promote
genomic instability in cells through the production
of reactive oxygen species (ROS).
43.
44.
PRE-CANCEROUS CONDITIONS
Chronic
atrophic gastritis of pernicious anemia .
Solar keratosis of the skin.
Chronic ulcerative colitis.
Leukoplakia of oral cavity , vulva and penis.
Some benign tumor like villpous adenoma of
colon, liomymoma.
47. Common tumors of male are:
Ca prostate
Ca lung
Ca colon / rectum
Common tumors of female are:
Ca breast
Ca cervix
Tumors of ovaries
Ca lung
48.
Common tumors due to alcohal
Ca oropharnx
Ca larynx
Ca esophagus
Ca liver
Common tumors due to ciggrate smoking
Ca lung 90%
Ca mouth
Ca pharynx
Ca larynx
Ca esophagus
Ca parncreas
Ca gall bladder
49.
Common tumors of children
Acute lymphoblastic leukemia
Neuroblastoma
Willm’s tumor
Retinoblastoma
Rhabdomyocarcoma
Common tumors of old age
Ca prostate
Leukemias
Ca pancreas
50. Normal physiology of cell proliferation
Following steps
Growth factor
The binding of growth factor to its specific receptors
generally located on the cell membrane.
Transient and limited action of the growth factor
receptor.
Transmission of transduced signal across the cytosol
to the nucleus via second messengers or by signal
transduction molecules that directly activate
transcription.
Induction and activation of nuclear regulatory factors
that initiate DNA transcription .
51. GENES
Genetic damaged (or mutation) by environment
agents such as chemicals, radiation, virus or it may
be inherited .
Tumor is formed by clonal expansion of a
single precursor cells that has incurred the
genetic damage.
Four classes of normal regulatory gene.
Growth promoting protooncogene.
Growth inhibitory tumor suppressor gene.
Gene that programmed cell death (apoptosis).
Gene involve in DNA repair .
52.
Oncogene .
Protooncogene.
That promote autonomus cell growth.
Normal cellular counter part of oncogene.
Protooncogene converted into cellular oncogene (Cone).
That are involved in disease development.
Oncoprotein .
Product of oncogene is called as oncoprotein.
53.
54. SEVEN FUNDAMENTAL CHANGES IN CELL
PHYSIOLOGY TO PRODUCE MALIGNANCY
Self sufficiency in growth signals –proliferation
without stimuli
Insensitivity to growth inhibitory signals
Tumor may not respond to molecule that are inhibitory to
the proliferation of normal cell.
E.g. transforming growth factor β (TGF β).
Direct inhibitor of cycline dependant kinase.
Evasion of apoptosis
Tumor resistance to programmed cell death by
inactivation of P53.
55.
Defect in DNA repair –
By carcinogens or unregulated cellular proliferation .
Limitless replicate potential .
Unristicted proliferative capacity
By maintance of telomer length and function.
Sustained angiogenesis .
By vascular endothelial growth factor (VEGF) .
Ability to invasion and metastasis
56.
57.
58. 1.
Growth factor
2.
Growth factor receptor
3.
Signal transducing protein
4.
Nuclear regulatory factor initiate DNA transcription
5.
Cell cycle
59. 1.
GROWTH FACTOR:
Many cancer cells acquire growth self sufficiency
by synthesize some growth factor (PDGF, TGFα)
Glioblastoma secrete PDGF and sarcomas TGF
α)
Growth factor gene it self not altered or muted but
the product of other oncogene (e.g. RAS) caused
over expression of growth factor gene, therefore
secrete large amount of growth factor
60. 2. GROWTH FACTOR RECEPTORS:
Mutations and pathologic over expression of normal
form of growth factor receptor have been detected in
several tumors
Over expression of ERBBI (EGF receptor) is over
expressed in 80% of squamous cell carcinoma of lung
HER2 receptor is amplified in 25-30% of breast cancer,
adenocarcinoma of lung, ovary and salivary gland
61. 3. SIGNAL TRANSDUCING PROTEIN:
Signal protein receive signal from activated growth
factor receptors and transmit them to nucleus
Two important members RAS and ABL
30% of all human tumor contain mutated version of
RAS
Ca colon and ca pancreas, mutation of RAS is high
62. RAS GENE:
When normal cell stimulated through growth factor
receptor, inactivated (GDP-bound) RAS is activate to
GTP bound state
Activated RAS transmit signals to the nucleus
Mutation of RAS, permanently activated leading to
continuous stimulation of cells without external stimuli
RAS gene is commonly activated by point mutation
63. 4. NUCLEAR TRANSCRIPTION FACTOR :
All signal transcription factors enter the nucleus and
increase mitotic activity
Excessive, abnormal growth occur when mutation of
gene responsible for DNA transcription
Most common oncogene are MYC, MYB, JUN, FOS
and REL have been localized to the nuleus
MYC gene is most commonly seen in human tumor
64. MYC gene:
MYC protooncogene is expressed in all cells
MYC protein is induced rapidly when quiescent cell
receive signal to divide
MYC protien bind to DNA causing transcription activation
of several growth related gene (including cyclin dependent
kinase)
Oncogene version of MYC gene are over expressed and
contribute to sustained proliferation
Translocation of MYC gene seen in burkitts’ lymphoma, Bcell tumor
Amplification of MYC is seen in breast, colon, lung and
many other cancers
71. Cell Cycle:
After all growth promoting stimuli, the entry of
quiescent cell into cell cycle
Mutation of cyclin and CDKs favour excessive
proliferation
Cyclin D and CDK4 are commonly seen in neoplastic
transformation
Cyclin D over expression is seen in beast,
Oesophagus, liver and lymphoma
Amplification CDK4 gene occurs in melanoma,
sarcoma and glioblastoma
72.
73. Insensitivity to growth inhibitory signals
(tumor suppressor gene)
The growth of cell has to be controlled by many
external signal to maintain the steady state
(homeostasis) .
Failure of growth inhibition is one of the fundamental
alteration in the process of carcinogenesis .
The genes brakes cell proliferation are called as tumor
suppressor gene.
The protein that apply brakes to cell proliferation are
the product of tumor suppressor gene.
74.
75. RB gene (Retinoblastoma )
First tumor suppressor gene
RB gene discover from Retinoblastoma (childhood
tumor)
RB gene is also seen in breast cancer, small cell
carcinoma of lung, bladder carcinoma.
RB gene product is a DNA binding protein that is
expressed in every cell.
The main role of RB gene is active
hypophosphorylated and inactive hyper
phosphorylated state.
76.
In it s active state, RB brake the cell proliferation
from G1 to the S phase of the cell cycle.
If RB protein is absent or mutation , the molecular
brakes on the cell cycle are released and cell move
into S phase.
Various growth factor promote the formation of the
D/CDK4 complex like EGF, TGFα, HGF, PDGF.
Growth inhibitor inhibit the above process (TGFβ,
P53, and other )
77.
78. P53 (Guardian of the genome)
Located on chromosome on 17P13 A, and it is the most
common target for genetic alteration in human tumors.
50% of human tumor contain mutations in this gene .
Most commonly seen in Ca lung, Ca breast, and Ca
colon.
P53 also called as gate keeper or molecular policeman
against the formation of cancer, that prevent the
propagation of genetically damage cells
P53 protein is a DNA binding proteins localized to the
nucleous.
79.
Main function is to control the transcription of several
other gene.
Mutation RB (transforming protein of several DNA virus)
and MDM2 degrade the formation of P53.
The main function of 53 proteins are cell cycle arrest
and initiation of apoptosis in response to DNA damage.
P53 apply emergency brakes when DNA is damage by
irradiation, ultraviolet light and chemicals.
P53 also help in the repair process directly by inducing
the transcription of GADD45 (growth arrest and DNA
damage ) which encodes proteins involved in DNA
repair.
80.
When DNA repaired successfully P53 activate
MDM2, whose product degrade P53, thus releiving
the cell cycle brake.
If DNA damage not successfully repair P53 send the
cell to the grave yard by inducing the activation of
apoptosis gene (BAX)
BAX binds to and antagonizes the apoptosis
inhibiting protein BCL-2 thus promote cell death.
In view of these activities P53 right fully called
‘guardian of genome’.
81.
82. APC gene
Tumor suppressor gene that responsible for down
regulation of growth promoting signals (β-catenin)
In the cell nucleous β catenin form a complex with
TCF (transcription factor) that up regulation of
cellular proliferation by transcription of cell promote
gene (MYC)
85. EVASION OF APOPTOSIS
Cell growth in regulated by growth promoting and
growth inhibitory gene, cell survival is conditioned by
gene that promote and inhibit apoptosis.
The accumulation of tumor cells may occur due to
mutation in the gene that regulated apoptosis.
BCL-2
BCL-2 protect cell from apoptosis
Translocation of BCL-2 results over expression
therefore protect tumor cells from apoptosis e.g. B-cell
lymphoma of follicular type.
86. P53
P53 Increase transcription of pro-apoptotic gene
such as BAX
Lack of P53 by mutation reduced apoptotic activity
MYC
MYC and BCL2 may collaborate in tumor genesis
MYC triggers proliferation and BCL2 prevent cell
death.
87. DNA repair defect and genomic instability in
cancer cell.
DNA damaging agents are ionizing radiation,
sunlight , dietary carcinogens and oxidative stress.
DNA of normal dividing cell is susceptible to
alteration resulting from error that occur
spontaneously during DNA replication . Such
mistake is not repair properly , therefore push the
cell into neoplastic transformation .
Those born with such defective gene, are at high risk
of developing cancer. These conditions are K/a
genomic instability syndrome.
DNA repair gene themselves are not oncogene, but
their abnormalities allow mutation in other gene
during the process of normal cell division.
88. Three types of DNA repair systems
Mismatch
repair
Nucleotide
excision repair
Recombination
repair.
89. Mismatch repair
Mismatch repair gene act as spell checkers of strand
of DNA . For example if there is some error in pair of
G with T , rather than the normal A with T. The
mismatch gene correct this defect.
Without these corrections errors slowly accumulate
in several gene including protooncogene and tumor
suppressor gene. Mutation in at least five mismatch
repair gene have been found in hereditary non
Polyposis cancer syndrome (HNPCC)
90. Defect in nuclutide excision repair
In xeroderma pigmentosum, defective DNA repair
genes, are at increased risk for the development of
skin cancer, when exposed to UV rays in sun light .
UV rays causes cross linking of pyrimidine residues ,
this preventing normal DNA replication . Such DNA
damage is repaired by the nucleotide excision repair
(NER) system . Several protein and gene are involve
in the NER, and on inherited loss of any one can
give rise to xeroderma pigmentosum.
91. Inherited disease with defect in DNA repair
by
hemologous recombination
In this DNA repair system two important gene
are BRCA1 , BRCA2
Mutation in two genes are seen in 80% of
familial breast cancer.
BRCA1 Mutation also produce ovarian cancer
in female and prostate cancer in male.
92.
BRCA2 mutation increase risk of Ca breast in
man and women and cancer of ovary,
prostate, pancreas, bile duct, stomach and
melanocyte.
Main function of these two gene are regulate
DNA repair
Cell that lack these genes develop
chromosomal breaks
BRCA1 is a part of multi protein complex that
is crucial for repair of double strands breaks
in chromosomes
93.
Limitless replicative potential . Telomerase
After fix number of division , normal cell become
arrested in non-dividing steps. It has been noted that
with each cell division some shortening of
specialized structure of cell called telomers at the
end of chromosome .
Loss of telomer resulting activation of P53
dependent cell cycle check point causing proliferate
arrest or apoptosis .
Germ cell telomer shorten is prevented by enzyme
telomerase
94.
Loss of telomerase means loss of replication ability .
In tumor cell reactivation of telomerase.
Telomerase is detected in more then 90% of
tumors .
Telomerase activity and maintain of telomer length
are essential for the replicative potential in cancer
cell.
95.
96. Development of sustained
angiogenesis
Tumor stimulate the growth of host blood vessels
called as angiogenesis.
Essential for supply a nutrient to the tumor.
Two factor produce by tumor cells are VEGF and
bFGF.
97.
98. Invasion and metastasis
Detachment (“ loosening up”) of the tumor cells from
each other.
Attachment to matrix components.
Receptors of lamina and fibronectin of ECM.
Degradation of ECM.
E. adherins.
Catenine.
MMPs (Matrix metaloprotenasis) – type IV colegenase.
Migration of tumor cells.
CD44.
99.
100.
101. WHY TUMOR SPREAD IN PARTICULAR
ORGAN OR TISSUE?
Adhesion molecule whose ligands are expressed on
the endothelial cells of the target organ.
Chemokines have important role in spread of tumor
in particular organ or tissue .e.g. some breast cancer
expressed the chemokine receptors CXCR4 and
CCR7 . Chemokines that bind to these receptors are
highly expressed in tissue to which breast cancer
commonly metastasize .
Some target organ may liberate chemoattractants
that tend to recruit tumor cell to the site.
104. CHEMICAL CARCINOGENESIS
- Initiations –exposure of cells to a sufficient dose of a
carcinogenic agents (initiator).
(DNA damage and mutation )
- Initiated cell is altered making it potentially
capable of giving rise to a tumor.
- Initiation is not sufficient for tumor formation.
- Promotor – these are chemicals which them selves
are
noncarcinogenic but induce
tumor in initiated
cells.
(Clonal expansion of mutated cells)
105.
106. INITIATION OF CHEMICAL CARCINOGENESIS
1.
1.
Direct acting compound
Do not require metabolic conversion to become
carcinogenic
2.
Indirect acting compound (Pro
carcinogene)
Which require metabolic conversion to become
carcinogenic
107.
108.
Carcinogenic are highly reactive electrophiles (have
electron deficient atom) that can react with
nucleophilic (electron rich) in the cell. These
reaction are non enzymatic and result in the
formation of covalent adducts (addition product)
between the chemical carcinogenic and a nucleotide
in DNA .
Electrophlic reaction may attack DNA, RNA and
proteins of target cell .
110. MICROBIAL CARCINOGENESIS
Viral carcinogenesis
DNA virus
The genome of oncogenic DNA form stable association with
host cell genome.The virus is enable to complete its
replicative cycle because the viral gene essential for
completion of replication are interrupted during the integration
of viral DNA .Thus virus can remain in a laten state for years.
Those viral gene that are transcribed early in the viral life
cycle (early gene) are important for transformation and are
expressed in transformed cells.
E.g.
111. HUMAN PAPILOMA VIRUS (HPV)
Benign
squamous papiloma (warts) .
Squamous cell carcinoma of cervix .
Oral and laryngeal cancer.
E6
and E7 protein product of HPV viral gene bind and
neutralize the RB and P53 suppressor gene .
E7
also interfere with P53 transcriptional activity and also
inactivate P21.
Net
effect of E6 and E7 is to block apopotsis and excessive
cell proliferation .
112. EPSTEIN - BARR VIRUS (EBV)
Burkitt’s lymphoma
Post- transplant lymphoproliferate disease
Primary central nervous system lymphoma is AID patients
Sub set of other AID related lymphoma
Sub set of hodgkin lymphoma
Nasopharyngeal carcinoma
LMP-1 gene (EBV encoded gene) act as oncogene, promote
B cell proliferation by activating signaling pathways.
LMP-1 also prevent apoptosis by activating BCL-2.
EBNA-2 EBV encoded gene –transactivate several host
gene including cyclin D and Src family genes.
113. HEPATITIS B VIRUS
Hepato cellular carcinoma
Mode of action of this virus in tumor production is
not fully known.
Chronic liver cell injury and regeneration, HBV
predisposes the cell to mutations, caused possibly
by environment agents e.g. dietary toxin
HBV encoded regulatory element called HBx.
HBx disrupts normal growth of infected liver cell by
transcripitional activation of several growth control
genes .
114. RNA virus
Retrovirus transform cell by two mechanism
1.
Acute transforming virus contain viral oncogenes,
transduced human protooncogenes .
2.
Slow transforming virus
Do not contain viral oncogene but proviral DNA are
found near a cellular oncogene . Under the
influence of a strong retroviral promotor, the
mutated or normal cell oncogene is over
expressed. This mechanism of transformation is
called insertional mutagenesis e.g. Human T – cell
leukemia virus type I (HTLV-1)
115. HTVL-1
Produce T cell leukemia / lymphoma
HTLV-1 has tropism for CD4+ T-cell and this subset of T
cells is the major target for neoplasm trasnformation.
Infected T cell spread via sexual intercourse, blood
product and breast feeding.
Pathogenesis
HTLV-1 infected many T-cells causes polyclonal
proliferation activated by TAX gene.
TAX neutralize growth inhibitory signals by attaching
P53 .
Ultimately monoclonal T leukemia / lymphoma.
116. HELICOBACTER PYLORI
Peptic ulcer
Gastric carcinoma .
Gastric lymphoma (B-cell origin)
H.Pylori infection leads to the formation of H.Pylori
reactivity T-cells which causes polyclonal B cell
proliferation .
Gastric carcinoma ------ first chronic gastritis followed by
gastric atrophy, intestinal metaplasm of the epithelial
linning, displasia and cancer.
This sequence takes decades to complete and occurs in
only 3% of infected patient .
117. Tumor Immunity
(host defense against tumor immunity)
Tumor antigens
Antigen that elicit immune response.
Two types
Tumor specific antigen
Present on tumor cell and induce immune
response to a tumor it self
e.g. testicular carcinoma
melanoma
medullary carcinoma of breast.
118. Tumor associated antigen.
These are present in tumor cells and some normal
cells. they do not induce immune response but their
detection is of value in detection of certain tumor.
e.g. 1. Embryonic antigen (oncofetal antigen) .
(a) alpha fetoprotein .
(b) carcinoembryonic antigen.
2. Differentiation antigen
produced by tumor cell at a specific
differentiation
stage
eg. CD10 –expressed in B cell lymphoma,
prostatic specific antigen – Ca prostate .
119. Anti-tumor effecter mechanisms
1.Cytotoxic T- lymphocyte (CTLs)
Play a protective role against virus associated neoplasma
e.g. EBV induced Burkitt’s lymphoma
Important role for CD8+ cytotoxic T cells in tumor immunity
CTLs recognized peptide antigen present on the tumor cell
surface by MHC class I molecule.
2.Natural Killer cells (NK)
Lymphocyte that destroy tumor cells without prior sensitization
IL-2 activate NK cells and lyse the tumor cells
NKG2D protein expressed on NK cells and some T lymphocyte
are important triggering receptors. They recognize antigen
expressed mainly on tumor cells.
NK cells can also participate in antibody dependant cellular
toxicity.
120. 3. Macrophages
Activation of macrophages by interferon gamma. this
cytokine produce by T-lymphocyte and natural killer
cells.
Activated macrophages kill tumor cell by production
of reactive oxygen metabolites or by secretion of
tumor necrosis factor (TNF) .
4. Antibodies.
Antibodies formed by various tumor antigen .
Antibody kill tumor cell by activating complement or
by antibody dependant cell mediated cytotoxicity .
121. Immune surveillance
Prevention of tumor from immune system
1.
Selective out growth of antigen negative variants,
During tumor pregression, strongly immunogenic sub
clone may be eliminated.
2.
Loss or reduced expression of histo compatibility
antigen .
3.
Lack of costimulation
Sensitization of T cell require two singles, one by
forign peptide presented by MHC and the other by
costimulatory molecules . Tumor cell do not
expressed constimulatory molecule (B7-1). B7-1
prevents sensitization of T cell but also T cell under
go apoptosis
122. CLINICAL FEATURES OF TUMOR
Local pressure on adjacent structure
Hormone or hormone like substance release from
tumors ------ para neoplastic syndrome
Bleeding and infections, when tumor ulcerated
E.g. Pressure of adenoma of pitutray gland -----Hypopitutrism
Neoplasm of gut ------ Intestinal obstructions
E.g. tumors of skin and gut
Symptoms result from rupture or infarction
Cachexia or wasting
123. Cancer cachexia
Progreessive loss of body fat and lean body mass
accompanied by profound weakness , anorexia and
anemia .
Cachexia result for the action of soluble factor such
as cytokines produce by tumor and by the host in
response to the tumor.
TNF
IL-1
Interferon gamma
124. PARANEOPLASTIC SYNDROME
Symptoms complex other than cochexia that appear
in patient of cancer due to secretion of hormones or
hormone like substances from tumors.
Endocrinopathy ------ Ectopic hormone production
125.
126. GRADING AND STAGING OF TUMOR
Grading
Degree of differentiation of the tumor cell and
number of the mitosis within tumor.
1. Well
differentiated .
2. Moderate differentiated.
3. Poorly differentiated.
4. undifferentiated.
127. Staging
Staging of cancer is based on the size of the primary
lesion , spread of regional lymph node and presence
or absence of metastasis .
TNM system (UICC).
(a)
To --- Ca in situ .
T1 --- T4 size of primary tumor.
(b) N--- regional lymph node involvement
No,N1,N2,N3/
(c) M--- Mo no metastasis.
M1, M2 ---- metastasis.
1.
2. AJC system.
In this tumor are divided in to stage o – IV, incorporating , size
of primary lesion , as well as presence of nodal spread and of
distant metastasis .
128. LABORATORY DIAGNOSIS OF
CANCER
Histologic and cytologic methods
Histologic
examination is the most important method of
diagnosis is greatly aided by
Availability of all relevant clinical data.
Adequate preservation and sampling of the specimen.
In some cases examination of the frozen specimen to
detect cell surface receptors.
In addition to the usual fixed and paraffin embedded
section, quick frozen secretion are employed to obtain a
rapid diagnosis while the patient is still under
129. FINE NEEDLE
ASPIRATION
Fine needle aspiration involves aspiration of cell
and fluids from tumors or masses that occur in
readily palpable sites e.g, breast thyroid lymph
nodes.
The aspiration cells are smeared stained and
examined.
130. CYTOLOGIC PAPANICOLAOUS
SMEARS
Cytologic or papanicolaou smear involve
examination of cancer cell that are readily shed
exfolitive cytology is ude most commonly in the
diagnosis of dyplasia carcinoma in situ and
invasive cancer of uterine cervix and tumors of
the stomach bronchus and urinary bladder.
Interpretation is based chiefly in changes in the
appearance of individual cells.
131.
132. IMMUNOCYTOCHEMISTR
Y
Immunocytochemistry involves detection of cell
products or surface markers by monoclonal antibodies
.
The binding of antibodies can be revealed by
fluorescent labels or chemical reactions that result in
the generation of a colored product. This technique is
useful in the following settings.
Diagnosis of undifferentiated tumors .
catagerazaion of leukemaias
determination of site of origin of metastasis .
Detection of molecules that have prognostic or
therapeutic significance .
133. DNA probe analysis
DNA probe analysis involves polymerase chain reaction
(PCR)or FISH analysis.
This technique is currently used in the diagnosis of lymphoid
neoplasm due to association of these tumors with chloral
rearrangements of T –cells and B – cells antigen receptor
genes .
Detection of oncogenes e.g.N – myc in assessing the prognosis
of certain tumors .
Diagnosis of chronic myeloid leukemia by detection of bcr – abl
fusion gene product even in the absence of philadelphia
chromosome.
Specific translocation can distinguish b/w similar appearing
tumors e.g. small round cell tumors in children
134.
Heredetary predisposition to certain tumor
e.g breast cancer and endocrine
neoplasm can be detected by mutilational
analysis of BRC A – 1, BRC A-2 and RET
genes .
135. FLOW CYTOMETRY
Measurement of the DNA containt of tumor
cell by flow cytometry is useful due to
relationship b/w abnormal DNA content and
prognosis.
Flowcytometry is of value in the diagnosis of
leukemia and lymphoma .
136. TUMOR MARKERS
These are tumor derived are tumor associated molecules that
can be detected in blood or other body fluids.
They are not primary methods of diagnosis but help in the
diagnosis.
They are also valuable in determining the response to
therapy .
Examples :
Carcinoembryonic antigen (CEA) normally produced by fetal gut
, liver and pancreas, may be elaborated by Ca: colon ,
pancreas stomach and breast.
Alpha fetoprotein is normally produced by fetal yolk sac and
liver ,markedly increased in Ca: liver and testicular embryonic
carcinoma .
