Neoplasia 4 Lecture Flashcards
What is the site at which the tumor cell lodge and produces secondary growth influenced by?
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
Tumor antigens classification
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)
Tumor specific antigens
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
Tumor antigens
Tumor-specific shared antigens Differentiation antigens Antigens resulting from mutations Over-expressed antigen Viral antigens
Tumor specific shared antigens
Antigens are expressed on many tumor cells but not on ANY normal tissues
- MAGE-1
Differentiation antigens
Expressed selectively in some normal cells and in cancer cells derived from those cells
- Antigenic peptide derived from enzyme tyrosine
Antigens resulting from mutations
Derived from mutated protoncogenes and cancer-suppressor genes (tumor specific)
- p53, BCR-c-ABL
Over-expressed antigens
Molecules over expressed in tumor cells give rise to peptides recognized by CD8 T cells
- c-erbB2 (breast cancer)
Viral antigens
Derived from proteins encoded by oncogenic viruses
- HPV (cervical cancer)
Immunosurveillance
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
Tumors may escape immunosurveillance by?
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
Local and hormonal effects based on?
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)
Cancer Cachexia
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
Paraneoplastic Syndromes
Symptoms not directly related to the spread of the tumor or elaboration of hormones indigenous to the tissue from which the tumor arose
Endocrinopathies
Some nonendocrine cancers produce hormones or hormone-like factors
Hypercalcemia
Occur owing to resorption of bone resulting from the amplification of parathyroid hormone like peptides
Neuromyopathic
Peripheral neuropathies, cortical cerebellar degeneration, polymyopathy
Acanthosis nigricans
Pigmented lesions of the skin is frequently associated with visceral malignancy
- Gray-black patches of hyperkeratosis on skin
Thrombotic diatheses
Results from production of thromboplastic substance by tumor cells
- Increased coagulation cascade
Histologic grading of tumors
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
Grading is imperfect bc?
Different parts of the same tumor may display different degrees of differentiation
- may change as a tumor grows
Clinical staging of tumors
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
Methods of staging?
The Union internation contre cancer
The American Joint Committee systems
TNM system
N0: no lymph node involvement
N2: two lymph nodes metastasized
M0: no distant metastasis
M1: one site detected
AJC
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)
Proper histologic diagnosis is greatly aided by:
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
Fine needle aspiration
Involves aspiration of cells and fluids from tumors or masses that occur in readily palpable sites
Aspirated cells are smeared, stained, and examed
Cytologic (PAP) smears
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
Immunocyochemistry
Detection of cell products or surface markers by monoclonal antibodies
- Binding of antibodies can be revealed by fluorescent labels or chemical reactions
Molecular Analysis
DNA probes involves polymerase chain reaction or FISH analysis
- Probe towards the defective DNA
Flow cytometry
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
Tumor markers
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
How cancer cells escape detection and kiling?
Drug resistance
Expresses immune cell inhibitors
Resistanct to apoptosis even due to chemotherapy
Normal tissue specific gene expression is lost
Limited access
Drug resistance
Pump out drugs from cells faster than it can act
Expresses immune cell inhibitors
Fas-ligand, TGF-beta, others
Resistant to apoptosis even due to chemotherapy
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
Normal tissue specific gene expression is lost
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
Limited access
By drugs, immune cells to cancer cells within tumor
