EXAM 2 Neoplasms

Question 1

Two types of tumors

Answer 1

Benign and malignant

Question 2

Defining characteristic between benign and malignant tumors

Answer 2

Malignant cancer metastasizes: cancer doesn’t stay in one place

Question 3

Benign Tumor Clinical Behaviors

Answer 3

• Have “innocent” behavior
• Localized lesions
• Without spread
• Patient survival (typically)
• Surgically removable

Question 4

Malignant Tumor Clinical Behaviors

Answer 4

• Aggressive behavior
• Aka “cancer”
• Metastasis

Question 5

All Tumors’ Basic Components

Answer 5

1) Clonal expansion: All cancers originate from one malignant cell
2) Important factors: genetic instability and environmental factors
3) stroma cells in healthy tissue: provide structural support - In a tumor: cells are leaky

Question 6

Rule of Thumb for Benign Nomenclature

Answer 6

• rule is if they end up w/ __oma, they’re benign.

- But there are exceptions that are malignant: sarcoma, melanoma, lymphoma, mesothelioma

Question 7

Nomenclature for Benign Tumors

Answer 7

• Adenomas (glands)
• Cystadenomas (producing cystic mass)
• Polyp (projecting above the mucosa), macroscopically
• Papilloma (finger-like projections, microscopically)

Question 8

Nomenclature for Malignant Tumors

Answer 8

1) Sarcomas (mesenchymal cell origin)
2) Carcinomas (epithelial origin)
2a) Squamous carcinomas
2b) Adenocarcinomas

Question 9

Benign Characteristics

Answer 9

1) Well-differentiated: how closely tumor cells histologically and functionally resemble their normal cell counterpart
2) NO Local Invasion: develop a surrounding rim of condensed connective tissue, or capsule
3) NO METASTASIS

Question 10

Malignant Characteristics

Answer 10

1) Lack of differentiation is called anaplasia -> malignancy’s hallmark
2) Local Invasion: Malignant tumors are invasive and infiltrative, destroying surrounding normal tissues with no capsule
3) Metastasis: Invasion of lymphatics, blood vessels, or body cavities by tumor, followed by transport and growth of secondary tumor cell masses dislodged from the primary tumor. MOST IMPORTANT FEATURE

Question 11

Tumor Differentiation

Answer 11

1) Normal
2) Very mild/mild dysplasia: dysplasia = disorganized growth
3) Moderate dysplasia
4) Severe dysplasia
5) In situ carcinoma: marked dysplastic changes involving the entire thickness of the epithelium (basement membrane still intact)
6) Invasive carcinoma: entire epithelium is filled with the disorganized cells, Basement membrane has been invaded and now the cancer cells can go to the blood/lymph and go anywhere

Question 12

Nuclear to Cytoplasm Ratio

Answer 12

In a normal cell, the ratio of the nucleus to the cytoplasm is 1:4 or 1:6
In abnormal cell, the area the nucleus occupies in the entire cell to the cytoplasm in the entire cell is 1:1 or 1:2 (can barely see cytoplasm)

Question 13

Pathways of Tumor Spread

Answer 13

1) Body cavities and surfaces
2) Lymphatic
3) Hematogenous (blood): Metastasis follows the venous flow pattern; lung and liver common areas

Question 14

Emerging Characteristics

Answer 14

1) Deregulating Cellular Energetics: Cancer cells switch to glycolysis (even in aerobic situation) and
do it 100x faster than norm cells. Increase GLUT-1 expression/receptors. O2 status in the whole tumor varies, which is why it switches to glycolysis
2) Avoiding Immune Destruction: Cancer cells are able to be recognized by our immune system

Question 15

Enabling Characteristics

Answer 15

1) Genome Instability and Mutation

2) Tumor Promoting Inflammation

Question 16

The Warburg Effect

Answer 16

• High levels of glucose uptake and fermentation via aerobic glycolysis
• Metabolic reprogramming shares the growth factor signaling pathway: need to grow as fast as possible

Question 17

Progenitor vs Stem Cell

Answer 17

• Progenitor: committed to become a specific target tissue

- Stem: can become anything

Question 18

The Stem Cell-Like Properties of Neoplasms

Answer 18

• Limitless replicative potential
• Evasion of senescence
• Evasion of mitotic crisis

Question 19

Invasion

Answer 19

• Invasion of ECM

- Vascular dissemination and homing of tumor cells

Question 20

Invasion Steps

Answer 20

1) Tumor cells detach from each other because of reduced adhesiveness and attract inflammatory cells
2) Proteases secreted from tumor cells and inflammatory cells degrade the basement membrane
3) Binding of tumor cells to proteolytically generated binding sites and tumor cell migration follow

Question 21

Evasion of Host Defense

Answer 21

• *KNOW THE PICTURE ON SLIDE 17**
• Evasion: avoiding the host response
• Lack of T cell recognition of tumor
• Inhibition of T cell activation

Question 22

Acquired DNA damaging agents

Answer 22

• Chemicals
• Radiation
• Viruses

Question 23

Inherited mutations in genes

Answer 23

• Genes affecting DNA repair

- Genes affecting cell growth or apoptosis

Question 24

4 fundamental genes that are effected in genomic instability

Answer 24

1) P-53 genes (guardian of the genome/growth promoting genes)
2) inhib of tumor suppression genes (RB)
3) DNA repair genes
4) apoptotic genes

Question 25

P-53 Genes

Answer 25

arrests the cell in the G1 cycle so DNA can be repaired and go through S phase

Question 26

Cancer Development

Answer 26

1) Initiating mutation 2) **Acquisition of genomic instability** 3) Acquisition of cancer hallmarks 4) Further genetic evolution 5) Diagnosis: genetically heterogenous cancer

Question 27

Genomic Instability

Answer 27

-DNA repair pathways act indirectly by correcting spontaneous DNA errors -Inherited mutations in DNA repair proteins increases the risk of carcinogenesis -P-53 is mainly involved in DNA repair pathway There are certain genes P-53 has growth promoting characteristics as well

Question 28

Examples of Genomic Instability

Answer 28

- Familial breast cancer: Mutations in BRCA1 & BRCA2 - Ovarian or prostate cancers: Mutations in BRCA1 - Ovarian, prostate, pancreases and stomach cancers: Mutations in BRCA2

Question 29

Evolution of Colorectal Cancer

Answer 29

1) Normal Colon 2) Germ-line (inherited) or somatic (acquired) mutations of cancer suppressor genes (*first hit*) - mucosa at risk 3) Methylation abnormalities and Inactivation of normal alleles (*second hit*) - adenomas 4) Proto-oncogene mutations 5A) Wild type (not mutated) --> Oncogene-induced senescence 5B) Homozygous loss of additional cancer suppressor genes --> carcinoma

Question 30

Environmental Carcinogens

Answer 30

- Chemical carcinogens - Radiant energy - Oncogenic viruses and other microbes

Question 31

Neoplastic transformation brought about by chemicals is broadly divided into two stages:

Answer 31

1) Initiation | 2) Promotion

Question 32

Initiation

Answer 32

- Induction of **irreversible changes** (mutations) in the genome - Types: a. Direct-acting agents b. Indirect-acting agents

Question 33

Promotion

Answer 33

- Process of tumor induction in previously initiated cells - Short-lived, reversible, and non-tumorigenic by themselves - Oxidated damage, inflammation: causes more of the mutation and get cancer

Question 34

Initiation phase has 2 sub-categories:

Answer 34

- direct-acting genes: genes that don't need further metabolization and can cause cancer (directly causes damage) - Indirect acting genes: act on CYP-450 (need metabolization, ex is cigarette smoking)