Flashcards in MOD 11 Deck (78):
Which 4 cancers account for over half the incidence of all malignant neoplasms?
Lung, prostate, breast and bowel carcinomas.
In which age group are the majority of malignant neoplasms diagnosed?
Over 65s (only a small proportion in people up to 24).
In children younger than 14 which cancers are most common?
Leukaemias, central nervous system tumours and lymphomas.
Which cancers have a high (87% and over) 5 year survival rate?
testicular, malignant melanoma and breast cancer.
Which cancers have a low (15% and under) 5 year survival rate?
Oesophagus, lung and pancreas (only 3%)/
What cancer causes the most death in the UK (over double the amount than the second most common leading cause of cancer deaths)?
What factors need to be taken into consideration when predicting the outcome of a malignant neoplasm?
2. General health status
3. Tumour site
4. Tumour type
5. Grade (e.g. differentiation)
6. Tumour stage (e.g. tumour burden)
7. Availability of effective treatments
What does tumour staging measure?
The maligant neoplasm's overall burden.
What is the commonest method for assessing the extent of a tumour?
The TNM staging system - standardised across the world.
In the TNM staging system, what does T stand for? How many subdivision to T are there?
T refers to the size of the primary tumour. It is typically expressed as T1-T4.
In the TNM staging system, what does N stand for? How many subdivision to N are there?
N describes the extent of regional node involvement e.g. N0-N2.
In the TNM staging system, what does M stand for? How many subdivision to M are there?
M denotes the extent of distant metastatic spread. E.g. M0-M1.
How does the TNM staging system assess different types of cancer?
Each cancer has its own specific TNM criteria.
How is the TNM staging system used to come up with an ultimate stage (I-IV)? What does each Stage (I-IV) roughly describe the cancer?
The details of this conversion vary for each cancer type but in general:
Stage I: early local disease
Stage II: advanced local disesae
Stage III: regional metastasis (i.e. any T, and N and M1).
What special staging system is used for lymphoma? What does each stage (I-IV) represent?
Ann Arbor staging.
stage I: lymphoma in a single node region
Stage II: two separate regions on one side of the diaphragm
Stage III: spread to both sides of the diaphragm
Stage IV: indicates diffuse or diseminated involvement of one or more extra-lymphatic organs such as bone marrow or lungs.
Duke's staging system is a historical staging system that was used for which type of cancer?
In Duke's staging system what does A mean?
Invasion into but not through the bowel wall.
In Duke's staging system what does B mean?
Invasion through the bowel wall.
In Duke's staging system what does C mean?
Involvement of lymph nodes.
In Duke's staging system what does D mean?
What is the importance of cancer staging?
It measures the tumour's overall burden and therefore is a powerful predictor of survival.
List some features of cells with worsening differentation:
1. Increased nuclear size
2. Increased nuclear: cytoplasmic ratio
3. Increased nuclear staining (hyperchromasia)
4. More mitotic figures
5. Pleomorphism: increased variation in size and shape of cells and nuclei.
What features of cells are used to grade tumours in the Bloom Richardson grading for breast cancer (G1-G3)?
1. Number of tubules
2. Number of mitotic figures
3. Nuclear polymorphism (variation in size and shape of nuclei).
In grading of squamous cell carcinoma and colorectal carcinoma, what do G1-G4 typically describe?
G1 = well-differentiated
G2 = moderately differentiated
G3 = poorly differentiated
G4 = undifferentiated or anaplastic.
What is meant by anaplastic?
When cells have lost so much differentiation that thy no longer morphologically resemble any tissue.
What is the importance of tumour grade?
It is more important for planning treatment and estimating prognosis in certain types of malignancy, such as soft tissue sarcoma, primary brain tumours, lymphomas and breast and prostate cancer.
What types of cancer treatment are available?
4. Hormone therapy
5. Treatment targeted to specific molecular alterations
6. (Immune system targets have recently shown promise)
What is the mainstay treatment for most cancers?
What determines the treatment used for a cancer?
1. The type of cancer
2. The cancer stage.
What is adjuvant treatment?
Treatment given AFTER the surgical removal of a primary tumour, to eliminate subclinical disease.
What is neoadjuvant treatment?
Treatment given to reduce the size of a primary tumour PRIOR to surgical excision.
Why is radiotherapy given in fractionated doses?
When given in multiple, small doses the effect of radiotherapy better differentiates between cancer cells and normal cells.
What types of radiation are used in radiotherapy?
X-rays or other types of ionising radiation.
Why does radiotherapy kill rapidly dividing cells (especially cells in G2 of the cell cycle)?
High doses of radiation cause either:
1. Direct DNA damage
2. Indirect DNA damage (induced by free radicals)
That is detected by cell cycle checkpoints, triggering apoptosis. Double-stranded DNA breaks cause damaged chromosomes that prevent M phase from completing properly.
List some classes of drugs that are used for chemotherapy:
2. Alkylating and platinum-based drugs
4. Plant-derived drugs
How do antimetabolites drugs work?
They mimic normal substrates invovled in DNA replication (e.g. fluorouracil mimics the DNA base uracil).
How do alkylating and platinum-based drugs work?
They cross-link the two strands of DNA (e.g. cyclophosphamide and cisplatin).
How do antibiotics work in chemotherapy?
They act in several different ways, e.g.:
1. Doxorubicin inhibits DNA topoisomerase, which is needed for DNA synthesis
2. Bleomycin causes double-stranded DNA breaks.
Give an example of a plant-derived drug used in chemotherapy. How does it work?
Vincristine. It blocks microtubule assembly and interferes with mitotic spindle formation.
Why do you get side-effects, such as hair loss, anaemia, mucositis and an increased risk of infections?
Chemotherapy is non-specific. It effects all rapidly dividing cells, including labile cell populations like hair follicles, bowel epithelium and bone marrow.
Give an example of a hormone therapy that is used to treat some breast cancers? How does it work?
SERMs (selective oestrogen-receptor modulator), e.g. Tamoxifen, are used to treat hormone receptor-positive breast cancer. It works by binding to oestrogen receptors and preventing oestrogen from binding.
What is the effect of oestrogen on breast tissue?
It plays a role in breast development and pregnancy by inducing the ductal component of breast development, as well as for causing fat deposition and connective tissue growth. It is also indirectly involved in the lobuloalveolar component, by increasing progesterone receptor expression in the breasts and by inducing the secretion of prolactin.
Give an example of a hormone therapy that is used to treat prostate cancer?
Give an example of a type of treatment that is targeted to specific molecular interactions that is used in some types of breast cancer:
A quarter of breast cancers have gross over-expression of the HER-2 gene. Herceptin is a drug that specifically blocks HER-2 signalling.
What is the effect of HER-2 signalling on cancer cells?
HER-2 is a tyrosine kinase receptor. Activation of it causes autophosphoryation and intracellular signalling cascades which promote cell proliferation and oppose apoptosis. The HER-2 gene is therefore a proto-oncogene.
Give an example of a type of treatment for chronic myeloid leukaemia which is targeted to specific molecular interactions. How does it work?
Imatinib is a drug that inhibits a fusion protein (caused by a chromosomal rearrangement - translocation producing a 'Philadelphia' chromosome). The fusion protein is part of a tyrosine kinase signalling pathway and is always 'switched on', causing the cell to divide uncontrollably.
What is the use of tumour markers?
Although some have a role in diagnosis, in general they are useful for monitoring tumour burden during treatment and follow-up.
Human chorionic gonadotrophin is a tumour marker for which type of tumour?
Oncofetal antigens are a tumour marker for which type of tumour?
Alpha fetoprotein is released by hepatocellular carcinoma.
What are oncofetal antigens?
They are proteins which are typically present only during fetal development but are found in adults with certain kinds of cancer.
What tumour marker is released by prostate carcinoma?
Prostate-specific antigen (PSA), though this is also released in BPH and prostatitis.
The mucin/glycoprotein CA-125 is a tumour marker for which type of tumour?
What is the purpose of cancer screening?
To detect cancers as early as possible when the chance of cure is highest.
What are some problems with cancer screenign?
1. Lead time bias
2. Length bias
3. Over diagnosis.
What national screening programmes are established in the UK?
Cervical, breast and bowel cancer screening.
What is lead time bias?
This is a bias that screening can cause. By catching a cancer earlier it can make it look like survival rate for that cancer has increased erroneously.
What is length time bias?
Rapidly growing tumours often present and are diagnosed before screening, therefore screening is more likely to pick up slow-growing tumours.
What is over-diagnosis?
This is the idea that screening can diagnose people with a cancer (or other condition) that ultimately will not be the factor that causes them morbidity and death. In these instances the diagnosis is not helpful.
What is the commonest cause of cancer death in the UK?
What is another name for nephroblastoma?
What is the name of a malignant tumour of skeletal muscle?
What type of lung tumour is most often associated with ectopic production of ADH?
Small cell carcinoma.
What type of cancer is associated with Epstein-Barr virus?
What is Ewing's sarcoma?
A rare type of cancer that usually affects the bones of children and adolescents.
What type of cancer is assoiciated with Aspergillus flavus?
A. flavus produces aflatoxins and is associated with hepatocellular carcinoma.
What is Kaposi's sarcoma?
A tumour, often within the skin and frequently associated with HIV infection and human herpes virus 8.
What is the name of a benign tumour of melanocytes?
Naevus (moles or birthmarks).
What type of cancer is associated with asbestos exposure?
What is the name of a malignant tumour of blood vessels?
What is the name of a benign tumour of cartilage?
Which tumour can produce 5-HT (serotonin)?
Carcinoid tumour (a rare cancer of the neuroendocrine system that is usually found within the bowel or appendix).
Name a tumour of the thyroid gland that can produce calcitonin?
Name a tumour marker of phaeochromocytomas:
Vanillyl mandelic acid.
Name a tumour marker of choriocarcinoma:
Often produces human chorionic gonadotropin.
Name a cancer of the skin that rarely metastases?
Basal cell carcinoma.
What type of tumour marker does colon cancer produce?
CEA (carcinoembryonic antigen).
What type of tumour is usually benign in the ovary and malignant in the tesits?