Pathology: Principles Of Neoplasia Part Ii

Front 1

What is the carcinogenicity of chemical agents dependent on?

Back 1

The dose
(multiple fractional doses over time have the same effect as a comparable one-time dose)

Front 2

What is it called when 2 chemical agents act synergistically to induce cell transformation (normal--> neoplastic)?

Back 2

Co-carcinogenesis

Front 3

Most chemical substance require METABOLIC activation for conversion into ________ ________.

Back 3

Ultimate carcinogens
(most are metabolized by CYP450-dependent mono-oxygenases in the liver)

Front 4

What are the 4 stages of transformation from a normal cell to a neoplastic cell?

Back 4

1. Initiation
2. Promotion
3. Conversion
4. Progression

Front 5

What stage of cell transformation occurs when DNA strands break, DNA methylation takes place, or when DNA repair is hindered.

Back 5

Initiation

Front 6

Do initiators stimulate cell division?

Back 6

NO.

They simply alter DNA or inhibit DNA repair mechanisms.

Front 7

Do initiated cells have growth autonomy?

Back 7

NO.

Front 8

Do initiated cells have unique, readily identifiable genotype or phenotype markers?

Back 8

NO.

Front 9

What kind of cells do chemical promotors induce?

Back 9

Previously initiated cells.
(They CANNOT cause neoplastic transformation in non-initiated cells).

Front 10

What type of chemical transforming factors induce clonal proliferation of initiated cells?

Back 10

Chemical PROMOTERS.

Front 11

When are transformed cells no longer dependent on the promoters for proliferation?

Back 11

When the cells become CONVERTED.
(they can now grow autonomously)

Front 12

During which stage of cell transformation does clonal evolution and heterogeneity occur?

Back 12

Progression

Front 13

How can ionizing radiation induce neoplastic transformation?

Back 13

Induces genetic mutation within the cell
(inactivates enzymes, alters proteins, causes chromo breakage, translocations, and point mutations)

(radiation can also inhibit cell-mediated immunity and therefore tumor surveillance).

Front 14

How can viruses induce neoplastic transformation?

Back 14

They can directly rearrange the structure or alter the expression of the host cell genome.

Front 15

Describe some characteristics of malignant cells.

Back 15

1. Increased rate of stem cell renewal
2. Loss of contact inhibition
3. Achorage independent growth
4. Less cohesive
5. Immortal
6. Develop invasive properties
7. Metastatic potential
8. Transplantability

Front 16

How does the "ras" family of oncogenes appear to influence the cell?

Back 16

Enhances signal transduction

Front 17

How does the "myc" family of oncogenes appear to influence the cell?

Back 17

Seems to make cells more responsive to growth factors controlling CELL PROLIFERATION and appears to confer immortality to the cell line.

Front 18

What is the role of the p53 tumor suppressor gene?

Back 18

This gene becomes very active after DNA damage.
It codes for a protein that binds to damaged DNA and INHIBITS CELL MITOSIS until the damaged DNA can be repaired.
If damage cannot be repaired, p53 INDUCES APOPTOSIS

Front 19

T or F

Neoplasia resulting from tumor suppressor gene inactivation is more common in inherited neoplasia vs acquired neoplasia.

Back 19

TRUE.

If you inherit one mutated allele (which will be present within ALL of your cells) the likelihood of a mutation occurring in the second allele is actually very high--so high that inherited mutations are considered to be "autosomal dominant."

Front 20

Which type of neoplasia (inherited or acquired) will most likely result in SOLITARY or unilateral tumors.

Back 20

Acquired.

(Inherited neoplasia has a greater tendency to develop MULTIPLE or bilateral tumors).

Front 21

Can a single oncogene transform normal cells into neoplastic cells?

Back 21

NO.

More than one oncogene may be involved, w/ each one supplying some of the functions required for the neoplastic conversion.

Front 22

Activation of oncogene = _________ of tumor suppressor genes.

Back 22

SUPPRESSION.

Front 23

What type of cellular adaptation stages are commonly seen during the gradual transition of normal cells to neoplastic cells?

Back 23

*Dysplasia (pre-neoplasia)
Hyperplasia
Metaplasia

Front 24

The propensity of tumor cells to reproduce may be the result of what kind of genetic alterations?

Back 24

Oncogene activation
(tumor suppressor inactivation)

Front 25

Evidence suggests that most tumors are of the ______ origin.

Back 25

Monoclonal
(a single cell from normal or neoplastic tissues becomes neoplastic at a specific level of differentiation and the clonal derivatives of that cell produces the neoplasm).

Front 26

Do most tumors have a tendency to mature (differentiate) as they divide?

Back 26

NOOOOooooo.

Usually there is an increase in the proportion of STEM CELLS undergoing replication and a corresponding decrease in the proportion of cells progressing to full end-stage maturation).

Front 27

T or F.

Most tumors have LOW Growth Fractions, and proliferation only slightly exceeds cell loss.

Back 27

TRUE.

Front 28

Which tumors are more susceptible to most anticancer drugs (tumors with high or low GFs)?

Back 28

HIGH Growth Fraction

Most cancer drugs act primarily on dividing cells, therefore those tumors which have a HIGH growth fraction are most vulnerable.
(Sadly, most tumors have a LOW Growth fraction).

Front 29

This refers to the proportion of cells within a tumor population that are in the proliferating pool.

Back 29

Growth fraction

Front 30

T or F.

Tumor growth is dependent upon vascularization.

Back 30

TRUE!

Front 31

Would you expect a tumor with a greater degree of angiogenesis to be more aggressive or less aggressive?

Back 31

MORE AGGRESSIVE.
(poorer prognosis for patient)

Front 32

As the tumor increases in size, what happens to the growth rate?

Back 32

Slows down
(due to diminished blood supply, competition for metabolites)

Front 33

What happens to an increasing proportion of tumor cells as the tumor enlarges?

Back 33

More and more tumor cells drop out of the mitotic cycle
(either due to necrosis or by entering into prolonged G1 or G0 phases of the cell cycle

Front 34

T or F.

By the time a tumor has reached clinical detection, the cell population is usually still homogenous.

Back 34

FALSE.

As tumors develop, they can undergo clonal evolution. So by the time they are detected, they are typically HETEROGENOUS in respect to morphologic appearance, karyotype, degree of differentiation, invasiveness, and metastatic capabilities.

Front 35

Are differentiated or dedifferentiated cells more likely to have characteristics that enable them to spread?

Back 35

Dedifferentiated.

Front 36

T or F.

By the time most malignant neoplasms have become clinically detectable, it is likely that they have evolved several subclones with metastatic potential.

Back 36

TRUE.

(The earlier a cancer can be identified, the less likely it is that more aggressive subclones have developed)

Front 37

What type of tumor cells will develop a high invasive and/or metastatic potential?

Back 37

Cell clones with a high mutation rate.

Front 38

What are some characteristics of malignant cells that allow them to metastasize?

Back 38

They are able to attach, degrade, and penetrate basement membranes and interstitial connective tissue.

Front 39

Name 4 intrinsic factors that can contribute to neoplasia.

Back 39

1. Genetics
2. Race
3. Gender
4. Age

Front 40

Name 3 extrinsic factors that can contribute to neoplasia.

Back 40

1. Chemicals
2. Viruses
3. Radiation
(tissues exposed to environment have higher instances of malignancies)

Front 41

Describe 3 examples of viruses that can cause neopslasia?

Back 41

1. Human Papilloma Virus --> cervical cancer
2. Hepatitis C --> hepatocellular carcinoma
3. Epstein-Barr virus --> lymphoma

Front 42

Genes that produce tumors are referred to as..?

Back 42

Oncogenes

Front 43

What are some effects of oncogene activity?

Back 43

1. Increased synthesis of growth factors
2. Defective cell surface receptors
3. Increased # of receptor sites
4. Direct nuclear stimulation
5. Alteration of cytoskeleton

Front 44

Name 2 tumor suppressor genes.

Back 44

1. RAB-1
2. p53

Front 45

Name 3 extrinsic factors that can contribute to neoplasia.

Back 45

1. Chemicals
2. Viruses
3. Radiation
(areas exposed to environment have higher instances of malignancies)

Front 46

Describe 3 examples of viruses that can cause neopslasia?

Back 46

1. Human Papilloma Virus --> cervical cancer
2. Hepatitis C --> hepatocellular carcinoma
3. Epstein-Barr virus --> lymphoma

Front 47

Genes that produce tumors are referred to as..?

Back 47

Oncogenes

Front 48

What are some effects of oncogene activity?

Back 48

1. Increased synthesis of growth factors
2. Defective cell surface receptors
3. Increased # of receptor sites
4. Direct nuclear stimulation
5. Alteration of cytoskeleton

Front 49

Name 2 tumor suppressor genes.

Back 49

1. RAB-1
2. p53

Front 50

In the case of familial retinoblastoma, how many "hits" are required to have a loss of heterozygosity?

Back 50

"One hit"

Front 51

In the case of acquired retinoblastoma, how many "hits" are required to initiate neoplasia?

Back 51

"Two hits"

Front 52

If a patient has retinoblastoma in two eyes, would you assume the patient has a familial or acquired form of neoplasia?

Back 52

FAMILIAL.

Front 53

Why are areas of necrosis often seen near the center of a tumor?

Back 53

Although angiogenesis occurs, usually the vessels are not well formed, and the center of the tumor will be hemorrhagic and necrotic.

Front 54

If you can identify the major blood vessel that is supplying a tumor, what can you do to inhibit its growth?

Back 54

Embolize something into the blood vessel to cause an infarct.

Front 55

Describe the steps of invasion and metastasis.

Back 55

1. Basement membrane dissolution
2. Stromal invasion
3. Lymphatic/vascular invasion
4. Dissemination
5. Sites of preference

Front 56

How do malignant cells attach to and dissolve basement membranes?

Back 56

1. They may evolve mechanisms to secrete laminin or to produce tumor membrane receptors that binds native laminin
(laminin adheres tightly to the type IV collagen of the basement membranes)
2. Secrete proteases (type IV collagenase) to dissolve the membrane

Front 57

The ability of tumor cells to digest ground substance (collagen, glyoproteins, proteoglycans, and elastin) by the production of proteases and metalloproteinases is correlated with _________ potential.

Back 57

INVASIVE potential

Front 58

Why are lymphatic channels easily invaded by metastatic cells?

Back 58

They lack a basement membrane

Front 59

What type of innate immune cells have a chance to recognize and destroy disseminated tumor cells in the circulation?

Back 59

Natural killer cells

Front 60

How can clumps of tumor cells ward off immunologic recognition?

Back 60

They can produce procoagulants, which form "shields" of precipitated fibrin.
(May partly explain the hypercoaguable states seen in patients w/ disseminated cancer).

Front 61

What factors may contribute to a tumor's preference for one tissue over another?

Back 61

1. Tumor's ability to respond to tissue-specific chemotactic factors
2. Ability to adhere to tissue-specific endothelial cells
3. Ability to invade tissue-specific stroma

Front 62

Antigens found on neoplastic cells and NOT on normal cells.

Back 62

Tumor specific antigens

Front 63

Antigens found in normal cells but which are present in higher concentrations in tumor cells.

Back 63

Tumor associated antigens
(ex: differentiation antigens: beta HCG; oncofetal antigens: CEA, AFP)

Front 64

Refers to a microscopic PATHOLOGIC determination of tumor aggressiveness based on the degree of differentiation of the neoplastic cells and the number of mitoses as an estimate of the rate of growth.

Back 64

Grading

Front 65

What is the differentiation level of "Grade I" tumor?
What about Grade IV?

Back 65

Grade I: Well differentiated
Grade IV: undifferentiated (most dangerous)

Front 66

This refers to a CLINICAL and PATHOLOGIC determination of tumor aggressiveness based on the size of the neoplasm, the presence or absence of regional lymph node involvement, and the presence or absence of distant metastases.

Back 66

Staging

Front 67

What does the TNM staging system measure?

Back 67

Tumor size
Node involvement
Metastasis

Front 68

T or F.

In general, the smaller the tumor and the more localized it is, the better the prognosis.

Back 68

TRUE!

Front 69

Based on the TNM staging system, what does a 0 or an A represent?
How about a IV or a D?

Back 69

0/ A = localized tumor
IV/ D = metastatic tumor

Front 70

Why is it easier for a clump of tumor cells to metastasize than for a single tumor cell?

Back 70

A single tumor cell is more likely to be recognized and destroyed by immune responses.
A clump of cells, however, can produce procoagulants to form a shield and hide from the immune system

Front 71

How are tumors GRADED?

Back 71

Based on their morphology
(how well they are differentiated, shape of nucleus, etc.)

Front 72

How are tumors STAGED?

Back 72

Based on size of tumors, whether or not they have mestastasized to regional lymph nodes, or distant metastases.

Front 73

What type of tumors have the best prognoses?
Low Grade, Low Stage
OR
High Grade, High Stage?

Back 73

Low grade, low stage = best prognosis
(high grade, high stage = most aggressive)