Neoplasia 4 Lecture

Question 1

What is the site at which the tumor cell lodge and produces secondary growth influenced by?

Answer 1

Vascular and lymphatic drainage from the site of the primary tumors
Interaction of tumor cells with organ-specific receptors
Microenvironment of the organ or site (rich in protease inhibitors might be resistant to penetration by tumor cells) –> looking for area low in proteases

Question 2

Tumor antigens classification

Answer 2

Tumor-specific antigens (present only on tumor cells)

Tumor-associated antigens (present on tumor cells and also on some normal cells, do not evoke immune response)

Question 3

Tumor specific antigens

Answer 3

Readily demonstrated in chemically induced tumors
Composed of tumor-derived peptides that are presented on the cell surface by MHC Class I molecules and recognized by CD8 T cells

Question 4

Tumor antigens

Answer 4

Tumor-specific shared antigens
Differentiation antigens
Antigens resulting from mutations
Over-expressed antigen
Viral antigens

Question 5

Tumor specific shared antigens

Answer 5

Antigens are expressed on many tumor cells but not on ANY normal tissues
- MAGE-1

Question 6

Differentiation antigens

Answer 6

Expressed selectively in some normal cells and in cancer cells derived from those cells
- Antigenic peptide derived from enzyme tyrosine

Question 7

Antigens resulting from mutations

Answer 7

Derived from mutated protoncogenes and cancer-suppressor genes (tumor specific)
- p53, BCR-c-ABL

Question 8

Over-expressed antigens

Answer 8

Molecules over expressed in tumor cells give rise to peptides recognized by CD8 T cells
- c-erbB2 (breast cancer)

Question 9

Viral antigens

Answer 9

Derived from proteins encoded by oncogenic viruses

- HPV (cervical cancer)

Question 10

Immunosurveillance

Answer 10

Surveillance against tumors has be hypothesized

• Increased frequency of cancer in patients with congenital or acquired immunodeficiency
• Increased susceptibility to EBV infections and EBV- associated lymphoma in boys with x-linked immunodeficiency

Question 11

Tumors may escape immunosurveillance by?

Answer 11

Selective outgrowth of antigen-negative variants
Loss or reduction of MHC
Tumor-induced immunosuppression
Failure to sensitization because tumor cells do not express co-stimulatory molecules such as B7
Apoptosis of T cells because of tumor cells expressing Fas –> T cells die when attached to Fas

Question 12

Local and hormonal effects based on?

Answer 12

Location: intracranial tumors can expand and destory the remaining pituitary gland, giving rise to an endocrine disorder OR tumors of the GI may cause obstruction of the bowel or may ulcerate and cause bleeding
Production: tumors of endocrine glands may elaborate hormones (benign > malignant)

Question 13

Cancer Cachexia

Answer 13

Loss of body fat, wasting, and profound weakness
Multifactorial
- loss of appetite
- reduced synthesis and storage of fat
- increased moblization of fatty acids from adipocytes
- TNF-alpha can mimic some of the metabolic effects of tumors

Question 14

Paraneoplastic Syndromes

Answer 14

Symptoms not directly related to the spread of the tumor or elaboration of hormones indigenous to the tissue from which the tumor arose

Question 15

Endocrinopathies

Answer 15

Some nonendocrine cancers produce hormones or hormone-like factors

Question 16

Hypercalcemia

Answer 16

Occur owing to resorption of bone resulting from the amplification of parathyroid hormone like peptides

Question 17

Neuromyopathic

Answer 17

Peripheral neuropathies, cortical cerebellar degeneration, polymyopathy

Question 18

Acanthosis nigricans

Answer 18

Pigmented lesions of the skin is frequently associated with visceral malignancy
- Gray-black patches of hyperkeratosis on skin

Question 19

Thrombotic diatheses

Answer 19

Results from production of thromboplastic substance by tumor cells
- Increased coagulation cascade

Question 20

Histologic grading of tumors

Answer 20

The grade of malignant neoplasms provide a semi-quantitative estimate of the clinical gravity of a tumor

• Based on the degree of differentiation and the number of mitosis within the tumor (I-IV)
• • Higher the grade - more aggressive

Question 21

Grading is imperfect bc?

Answer 21

Different parts of the same tumor may display different degrees of differentiation
- may change as a tumor grows

Question 22

Clinical staging of tumors

Answer 22

The stage of malignant neoplasms provides a semi-quantitative estimate of the clinical gravity of a tumor
- Based on anatomic extent of the tumor; relevant to staging are the size of primary tumor and teh extent of local and distant spread

Question 23

Methods of staging?

Answer 23

The Union internation contre cancer

The American Joint Committee systems

Question 24

TNM system

Answer 24

N0: no lymph node involvement
N2: two lymph nodes metastasized
M0: no distant metastasis
M1: one site detected

Question 25

AJC

Answer 25

Divides all cancers into Stages 0 to IV - Incorportates size of the primary lesion, presence of nodal spread and distant metastases - Higher stages: larger, locally invasive and metastatic - Greater clinical value (staging)

Question 26

Proper histologic diagnosis is greatly aided by:

Answer 26

Availability of all relevant clinical data Adequate preservation and sampling f the specimen Examination of the frozen specimen to detect cell surface receptors Quick frozen sections are employed to obtain a rapid diagnosis while the patient is still underanesthesia

Question 27

Fine needle aspiration

Answer 27

Involves aspiration of cells and fluids from tumors or masses that occur in readily palpable sites Aspirated cells are smeared, stained, and examed

Question 28

Cytologic (PAP) smears

Answer 28

Cytologic or Pap smears involves exam of cancer cells that are readily shed Exfoliative cytology is used in the diagnosis of dysplasia, carcinoma in situ, and invasive cancer of the uterine cervix and tumor of the stomach, bronchus, and urinary bladder -False negative do occur

Question 29

Immunocyochemistry

Answer 29

Detection of cell products or surface markers by monoclonal antibodies - Binding of antibodies can be revealed by fluorescent labels or chemical reactions

Question 30

Molecular Analysis

Answer 30

DNA probes involves polymerase chain reaction or FISH analysis - Probe towards the defective DNA

Question 31

Flow cytometry

Answer 31

Measurement of the DNA content of tumor cells and cell surface antigens - Detection of cell surface antigens is of value in the diagnosis of leukemias and lymphomas

Question 32

Tumor markers

Answer 32

Tumor-derived or tumor-associated molecules that can be detected in blood or other body fluids and can help in choosing therapies - Hormone specific, oncofetal antigens (markers in developing fetus), or isoenzymes (change in expression), specific proteins, mucines, and new molecular markers based on proteins they observed

Question 33

How cancer cells escape detection and kiling?

Answer 33

Drug resistance Expresses immune cell inhibitors Resistanct to apoptosis even due to chemotherapy Normal tissue specific gene expression is lost Limited access

Question 34

Drug resistance

Answer 34

Pump out drugs from cells faster than it can act

Question 35

Expresses immune cell inhibitors

Answer 35

Fas-ligand, TGF-beta, others

Question 36

Resistant to apoptosis even due to chemotherapy

Answer 36

Population survives because the duration of treatment needs to be short enough that it does not kill normal cells, providing opportunity fro those in migration or circulation during treatment to "seed" a new site

Question 37

Normal tissue specific gene expression is lost

Answer 37

During de-differentiation or epithelial to mesenchyme transitions - Markers for these tissue specific genes can no longer detect or be used as targets even though they may have been over-expressed or originating tumor cells

Question 38

Limited access

Answer 38

By drugs, immune cells to cancer cells within tumor