Principles of Neoplasia Flashcards
• New, abnormal growth of tissue
– E.g. granulation tissue is new “normal” reparative growth
• Growth rate exceeds and is uncoordinated with the rest of the body
• Growth continues at the expense of the host
Neoplasm
– the study of tumors
– the diagnosis and treatment of cancer
Oncology:
: A hamartoma, not a true neoplasm
Hemangioma
Do most cancer cells grow faster than normal cells?
No
= the organ specific neoplastic cells – determines the neoplasm’s biologic behavior = the component from which the tumor derives its name
Parenchyma
= the connective tissue and blood vessels – Crucial to the growth of the neoplasm, since it carries the blood supply and provides support for the growth of parenchymal cells.
Stroma
• Abnormal cell growth that is uncontrolled, with the potential to invade or spread
to other parts of the body.
– Cause often lies in structural changes of DNA
Cancer
- Generates own growth signals
- Ignores signals not to grow
- Evades apoptosis: normal cells die when their time is up
- Limitless replication potential
- Angiogenesis: allows the tumor to sustain itself
- Invasion/metastasis: ultimate goal of cancer cells
Cancer cell
• The term means “to form backwards” •implies dedifferentiation, or loss of the structural and functional differentiation of normal cells • is the most extreme disturbance in cell growth
anaplasia
• Disorderly, but non-neoplastic proliferation • Encountered primarily in epithelium • A loss in the uniformity of individual cells and in their architectural orientation • Typically implies a precancerous condition, however, all do not necessarily progress to cancer
dysplasia
Which Type of cancer most commonly metastasize via lymphatic route to regional lymph nodes?
Carcinoma
Which Type of cancer most commonly metastasize via hematogenous route to lungs?
Sarcoma
Carcinomas metastasize via ____ route
Lymphatic
Sarcomas metastasize via ____ route
Hematogenous
Which type of cancer is mesenchymal?
Sarcoma
Which type of cancer is epithelial?
Carcinoma
____ is the development of tumor blood supply
Angiogenesis
Mixed tumor (pleomorphic adenoma) of parotid gland implanted during surgery
Transplantation:
Benign tumor of blood vessels
Heamngioma
WHich germ layer forms skin, oral mucosa, and adnexa?
Ectoderm
WHich germ layer forms muscle, fat, and bone?
Mesoderm
WHich germ layer forms lining of respiratory tract, GI, GU tracts, and liver and pancreas?
Endoderm
Carcinomas and adenomoas arise from what 2 germ layers?
Ecto and endoderm
Sarcomas arise from what germ layer?
Mesoderm
Osteomas and osteosarcomas arise from what germ layer?
Mesoderm
____ is a neoplasm
Tumor
A malignant neoplasm
Cancer
= a benign neoplasm of glandular epithelial origin
Adenoma
= a malignant neoplasm of glandular epithelial origin
Adenocarcinoma
= a malignant neoplasm of mesodermal tissue origin (connective tissue) –
bone, cartilage, smooth muscle, skeletal muscle, nerve, adipose tissue
Sarcoma
Tumors of lymphocytes
Burkitt lymphoma
Primitive tumor of kidney
Wilm’s tumor
Primitive tumor of bone
Ewing sarcoma
Do benign neoplasms transform into malignant?
Rarely
Are sarcomas more frequent in young or old?
Young
Are carcinomas more frequent in young or old?
Old
• Developmental, non-neoplastic overgrowth of normal tissue at a site where the tissues are normally expected to be found – Vs. Choristoma: • Developmental non- neoplastic overgrowth of normal tissue at an abnormal site abnormalities
Hamartoma
• A developmental, non-neoplastic overgrowth of normal tissue at a
site where the tissues are NOT normally expected to be found
• Heterotopic tissue
Christoma
• A tumor containing tissues from all three germ layers • Generally arise in gonadal tissues • Ovary most common • “Dermoid cyst” of the ovary – Benign cystic teratoma – May contain a variety of tissues including hair, teeth, bone, cartilage, thyroid, etc.
Teratoma
Using grading, is a well differentiated tumor grade 1 or 4?
1
Using grading, is a poorly differentiated tumor grade 1 or 4?
4
_____ is a measure of how localized or spread a malignant neoplasm is
-most important predictor of prognosis
Staging
Stage ____
– Single lymph node region
Stage 1
Stage ______
– Multiple lymph node regions
– Same side of diaphragm
Stage 2
Stage ______
– Disseminated disease
• Stage IV
Stage ______
– Multiple lymph node regions
– Both sides of diaphragm
• Stage III
A ____ grade tumor behaves aggressively
High grade
A ____ grade tumor behaves in an indolent manner
Low grade
What are the 2 groups of genes controlling growth?
Proto-oncogenes and TSG
At what point of the cell cycle do TSGs act?
G1 checkpoint
– normal function is to suppress cell proliferation
Tumor suppressor genes
– normal function is to promote cell proliferation
Proto-oncogenes
Is TSG dominant or recessive?
Recessive
Is proto oncogene, dominant or recessive?
Dominant
________ act as brakes on
cell proliferation
• Mutations must
create a loss-of-function if they are to have
an effect on cell proliferation
• Two copies of each gene, one paternal, one
maternal
• A loss-of-function mutation in one copy
leaves one functional copy
• A loss-of-function mutation in both copies
results in loss of all braking power, allowing
the cell to undergo unrestricted
proliferation
• act in a recessive
manner
Tumor suppressor genes
act as
accelerators for cell proliferation
• Mutations in must create
a gain-in-function if they are to have an
effect on cell proliferation
• There are two copies of each gene, one
paternal, one maternal
• A gain-in-function mutation in one copy is
all that is required to promote cell
proliferation
• A gain-in-function mutation in one copy
accelerates the cell cycle, allowing the cell
to undergo unrestricted proliferation
• act in a dominant manner
• Proto-oncogenes / oncogenes
The following are _______:
– P53
– Rb
TSG
The following are \_\_\_\_\_\_: – RAS: MEN IIb – cMYC: Burkitt lymphoma – bcr/abl fusion gene (Philadelphia chromosome): Chronic Myelogenous Leukemia (CML) – Neurofibromin: Neurofibromatosis
Protoncogenes
• No role in the normal cell cycle • DNA damage causes a rapid rise in protein • cell cycle arrest in G1, allowing time for DNA repair by binding the cyclin/CDK complex via p21 • If the DNA damage cannot be repaired, the cell is instructed to undergo apoptosis
p53
•\_\_\_ gene codes for a protein that acts as a brake, creating a checkpoint near the end of G1 • G1 checkpoint is a pause that assures DNA is repaired and the cell is prepared to enter the S phase • Mutations inactivate the protein loss of function and loss of a brake
Rb
Are TSGs or proto-oncogenes 2 hits to cause oncogenic activity?
TSGs
• Germ-line mutation in p53 (first hit) • A second hit eliminates all p53 activity • 25x the risk of cancer at usual sites as general population (lung, colon, breast ...) • Arise at earlier age and in multiple organ systems • Same cancers as the general population
Li-Fraumeni Syndrome
• Malignant neoplasm of retina • Familial form: multiple tumors in retinas of both eyes occurring in first few weeks of infancy – Germline mutation of one Rb allele (first hit) plus a somatic mutation of the second allele (second hit) • Sporadic form –single tumor in one eye sometime in early childhood – Both inherited alleles normal. Somatic mutation in both alleles (double hit)
Retinoblastoma
How many alleles must be mutated to turn a proto oncogene to an oncogene?
1 hit
• Normal function of \_\_\_\_ protein: receive a growth- promoting signal from cell surface receptors and forward the it through the cytoplasm to the nucleus • After the signal is sent by the active GTP form of it, it normally flips back to the inactive GDP form ending the signal • Mutations that abolish the ability to flip back to the inactive state result in a continuous signal to proliferate when no signal has been received from the cell surface
RAS
• _____ gene and its protein play an active role in shepherding the cell
through G1
• Cells lacking it will not progress to S phase
• Overexpression of it promotes inappropriate cellular
proliferation
– Burkitt lymphoma
c-myc
• Novel (new) protein (bcr/abl) formed with tyrosine kinase activity
• False signal sent to nucleus instructing it to enter the cell cycle and proliferate
• Acts as an oncogene
• Created by a 9 to 22 translocation that places the abl gene (chromosome 9) next
to the bcr region (chromosome 22)
Chronic myelogenous leukemia (Philadelphia chromosome)
BCR/ABL gene
• Translocation t(9:22) • Proto-oncogene abl on long arm chromosome 9(q34) • Transposed to bcr region (breakpoint cluster region) on chromosome 22(q11) Results in bcr-abl fusion gene Gene product is abnormal bcr-abl tyrosine kinase • Induces cell proliferation • Therapeutic intervention: – Gleevec (Imatinib mesylate) binds to the site of the tryosine kinase activity (tyrosine kinase
Philadelphia Chromosome –Chronic Myelogenous Leukemia (CML)
• Translocations, t(8:14) is the most common • c-myc proto-oncogene on chromosome 8 has a role in cell cycle progression • Immunoglobulin gene promoters cause overexpression of c-myc • Overexpression of c-myc oncogene promotes inappropriate cellular proliferation
Burkitt’s lymphoma
Normal function of \_\_\_\_ protein: receive a growth- promoting signal from cell surface receptors and forward the it through the cytoplasm to the nucleus
RAS
\_\_\_\_\_\_\_ facilitates conversion of RAS from active to inactive state • Loss of its function RAS tagged in active, signal- emitting state
Neurofibromin
\_\_\_\_\_\_ proto-oncogene codes for a tyrosine kinase receptor – mis-sense mutation of the receptor causes activation of the receptor protein causing the receptor monomers to dimerize • Mimicks the effect caused by binding of ligand • Activating (gain-in-function) mutation that sends a continuous signal to the nucleus to transcribe cyclins in the absence of growth factor
RET
Is cancer itself inherited?
No
Is an increased risk for cancer inherited?
Maybe
Autosomal recessive inherited mutations of
DNA repair genes
• Predisposition to UV-B associated
malignancies of the skin (Squamous cell
carcinoma, Basal cell carcinoma, Melanoma)
• Cancer not inherited, but susceptibility to
cancer is inherited
Xeroderma pigmentosum (XP)
• Chemicals: Polycyclic hydrocarbons
• Viruses
– Epstein-Barr Virus
– Human Papilloma Virus ***
– Must be transcriptionally active
• Carcinoma of uterine cervix: high risk strains inactivate p53, Rb TSGs
• Oropharyngeal squamous cell carcinoma
• Medical/dental diagnostic radiation: Thyroid shielding
• Nuclear radiation: Nuclear weapons, nuclear accidents
• Actinic (UV) radiation: Skin cancer
Carcinogens
– Symptoms/disease due to the presence of cancer in the body, but not due to
the local presence of cancer cells
Paraneoplastic syndrome
: Parathyroid hormone-related protein (PTHRP)
Hypercalcemia
: verrucous hyperkeratosis of skin
Acanthosis nigricans
– A pathologic state characterized by weight loss and anorexia that
accompanies some infections and neoplastic diseases
– weakness and wasting of the body due to severe chronic illness
– sustained production of tumor necrosis factor contributes to Cachexia
Cachexia:
