Hallmarks of Cancer CBCL 3 Flashcards
What features should we remember from the normal cervical tissue slide
The normal cervical tissue has a uniform epithelium layer. At higher magnification we can see that the epithelium is stratified squamous epithelium. The cells have increasing cytoplasm to nucleus ratio as they mature and go near the epithelial boundary.
This is why the cells at the basal epithelium appear darker.
What difference do you see in CIN (Cervix Intraepithelial Neoplasia)
The nuclei appear much darker in the stratified squamous epithelium. There is also increase in density of the cells as well as the cells show less cytoplasm, nuclei are larger and darker than normal
What do we see in Cervical SCC (Squamous Cell Carcinoma)
The cells have breached the basement membrane and they are invading the normal nearby cells. SCC is usually situated deeper in the tissue according to the slide that he showed to us and they are more eosinophilic (or pinkish). They have a characteristic experience marked by hyperchromasia.
What is another characteristic of Cervical SCC
Other types of carcinoma do not produce keratin
What are the 2 hallmarks of cancer
Proto oncogenes (tumor supressor genes) have to be evaded and oncogenes have to maintain proliferative signaling on a consistent basis
What are oncogenes
These genes lead to autonomous cell grwoth
Describe how an proto oncogene becomes an oncogene and how the oncoprotein changes
Mutation in a proto oncogene can lead to development of an oncogene. This gene makes oncoprotein that is different from protooncoprotein either in quality, quantity and/or function
How is an oncogene activated
It is activated by a GOF mutation. This requires to things:
- Change in structure
- Change in regulation of gene expression
What are the classes of oncogenes
- Growth factors
- Growth factor receptors
- Proteins involved in transduction
- Nuclear regulatory elements
- Cell cycle regulators which are CDKs and cyclins
What is the mechanism of action of oncogenes that act as growth receptors
They work in autocrine and paracrine loops (makes sense).
How does growth receptors work
By overexpression or mutation that makes them more active
What breast cancers have a poor clinical outcome? What is an effective therapy
HER-2 aplification breast cancers have a poor clinical outcome and they respond effectively to HER-2 therapy which is done by the drug called trastuzumab.
What type of breast cancer is caused by a faulty receptor
Human Epidermal Growth Factor Receptor 2 (HER-B2) causes breast cancer. HER-B2 is a member of a family of growth receptors
What proteins are invovled in cancer that are due to faulty signal trasnduction
- RAS proteins
- STAT/JAK proteins
- GTP binding proteins
- Non receptor tyrosine kinases
- NOTCH signal transduction
Which of these proteins are most common in casuing cancer
Mutations in the RAS proteins that beling to a family of G proteins
How is cancer associated with non receptor tyrosine kinases? What is the name of the specific cancer and what genes are involved?
Chronic Myelogenous Leukemia is associated with non receptor tyrosine kinases as the ABL gene is translocated such that the ABL gene fuses with the BCR gene. ABL/BCR are continuously activated leading to cancer.
This makes a chimeric protein that leads to the development of cancer.
How can JAK be associated with cancer
Point mutations in JACK can lead to self activation and continuous stimulation of the cytokine receptors
Name 2 examples and their respective mechanisms by which the nuclear regulatory elements can lead to the development of cancer
C-MYC overexpression due to translocation can lead to Burkitt lymphoma
N-MYC gene over amplification can lead to the development of neuroblastoma
Exaplin the mechanism of Burkitt Lymphma in detail
Burkitt lymphoma is a malignancy of B lumphocytes. All of the B lymphocytes are continuously making immunoglobulins. When the C-MYC gene comes translocates near the promoter region of the immunoglobulin gene, it is continuously turned on leading to the symptoms associated with Burkitt lymphoma
Exaplin the mechanism of neuroblastoma in detail
Instead of just one N-MYC gene, there are mutilple copies of this gene that leads to the development of neuroblastoma. This can be recognized by karyotyping or traditional form of DNA mapping that shows regions of double minutes
What is a fundamental difference in the mechanism of action of oncogenes and tumor supressor genes
For oncogenes, there is frequently a GOF mutation which requires mutation in only one of the alleles whereas in tumor suppressor genes both of the alleles have to supressed in order for the development of cancer
Two examples of tumor suppressor genes
P53 gene and Retinoblastoma (Rb) gene
How do you degrade or obsolete both of the tumor suppressor genes
- Deletion of that part of the genome
- Mutation in both of the genes
- Gene loss during chromsomal duplication
- Mitotic recombination
- Methylation of the promoter
- The gene’s protein can be degraded or it can be made disfunctional. Example is the action mechanism of the Human Papillae Virus which makes E6 and E7 proteins that inhibit tumor suppressor proteins
What is the most important check point in cell cycle? What is its mechanism
Rb. When it is phosphorylated it causes the release of E2F which allows the cell to enter the S phase from G1 phase
What cancer is asscoiated with Rb
Rb. it happens in the retina of the eye. Both of the genes have to be mutated in order to develop this cancer
What is the other common gene involved in cell tumor suppressor gene
TP53. It codes for the protein p53 which tells the cell to undergo apoptosis when the DNA is sufficiently damaged. Mutations with TP53 that leads to the development of cancer are resistant to chemotherapy since the cell doesnt know when to underogo apoptosis
What other gene is involved in cancer and which form of cancer is associated with it
APC gene is associated with colorectal cancer, normal APC binds and inhibits beta catenins which is part of a signalling pathway. Defects in APC or mutations in APC can lead to sporadic colorectal cancer
What are the 2 cells involved in the histopathology of neoplasia
Tumor parenchyma cells and the supportive stroma cells. Both cells are necessary for recruitment and growth
Define differentiation, pleomorphism and anaplasia
Degree to which tumor cells resemble cells of origin - differentiation
pleomorphism is he variance in size and shape
anaplasia refers to the lack of differentiation
What is grading
Terms like well differentiated, poorly differentiated is grading, it applies only to malignant neoplasms
Invasion and metastasis
Invasion refers to the growth of neoplasm from beyond the site of origin
Metastasis refers to the spread of neoplastic cells to a site distant from the origin
What is the difference in benign and malignant neoplasms
Benigns are localized, unable to invade or metastasise and generally have good clinical outcome and prognosis
Malignant neoplasms are cancers, they are able to invade other normal cells, they can metstasise and they generally have poor clinical outcomes and prognosis
How do you name these cancers
Benign are named as oma added to the end.
Malignant are named from what they are derived. If it is derived from epithelium it will be cancinoma, if from mesenchyme, sarcoma and if it is from hematopoeitic lymphoma or leukemia and finally if from melanocytes we call it melanoma
What is mixed tumor and teratoma
Teratoma is from the neoplasm of germ cells and mixed tumor is neoplasm from divergent differentiation
What are the characterisitics of benign neoplasm
It has smooth margins, it can be even capsulated, it has a unifrom composition and it has a lack of mitotic activity and we do not see alot of necrosis or death of normal cells
Explain the features of malignant neoplasms
