MoD: Tumours Flashcards
What are some histogenic classifications within tumours?
Epithelial cells- carcinomas
Connective tissues- sarcomas
Lymphoid/ haematopoietic organs- lymphomas/ leukaemias
What does the GRADE of a tumour measure?
How differentiated it is.
Well differentiated= low grade/ grade 1
Poorly differentiated= high grade/ grade 3
What does the STAGE of a tumour measure?
A measure of the extent of disease
Define metastasis
Spread of a tumour to sites physically discontinuous with primary tumour
(different pathways of metastasis…)
What is Direct seeding?
Neoplasm penetrates a natural open field without physical barriers eg)peritoneal cavity, pleural, pericardial, subarachnoid.
Can remain confined to surface of peritoneal structures without penetrating.
(different pathways of metastasis…)
What is Lymphatic spread?
Most common pathway
Pattern of lymph node involvement follows the routes of lymphatic drainage.
(different pathways of metastasis…)
What is Haematogenous spread?
Typical of sarcomas.
Bloodborne cells follow the venous flow draining site of the neoplasm. Often come to rest at the first encountered capillary bed.
Liver (portal) and lungs (caval) most frequently involved
What is the stroma and what does it provide?
A connective tissue framework that neoplastic cells are embedded in.
Provides: Mechanical support, intercellular signalling and nutrition.
What is a desmoplastic reaction?
Fibrous stroma formation due to induction of connective tissue fibroblast proliferation by growth factors from the tumour cells.
What does a stroma contain?
Cancer-associated fibroblasts
Myofibroblasts
Blood vessels
Lymphocytic infiltrate
Benign tumour of surface (non-glandular/non-secretory) epithelium?
PapillOMA
Benign tumor of glandular/ secretory epithelium?
AdenOMA
Malignant epithelial tumors?
Carcinomas (eg from secretory epithelium= adenocarcinoma)
Benign mesenchymal tumors?
-oma (preceded by tissue of origin eg from bone= osteoma)
Malignant mesenchymal tumors?
Sarcomas (prefixing with mesenchymal tissue of origin, eg malignant tumour of cartilage = chondrosarcoma)
What is the WHO Grading (I-IV) or CNS Tumours?
Grade I- tumors slow-growing, nonmalignant
Grade II- tumors relatively slow-growing, nonmalignant or malignant
Grade III- tumors malignant
Grade IV- tumors reproduce rapidly, aggressive malignant
What is a myeloma?
Tumor of the plasma cells
What is a hamartoma?
Benign, non-neoplastic tissue overgrowth.
Indigenous to site but disorganised mass. (eg lung hamartoma= bronchial epithelium and cartilage)
Examples of malignant tumours which have seemingly benign names?
Melanoma
Mesothelioma
Myeloma
Lymphoma
Name:
a) benign smooth muscle tumour
b) benign striated muscle tumour
c) benign adipose tissue tumour
a) Leiomyoma (if malignant= leiomyosarcoma)
b) Rhabdomyoma
c) Lipoma
In terms of carcinogens, what does genotoxic and non-genotoxic mean?
Genotoxic- can commonly modify or damage DNA (Initiators)
Non-genotoxic- induce proliferation and DNA replication (Promotors)
What are some examples of occupational exposure to carcinogens?
- –Workers in aluminium production/ coal/ coke production/ iron and steal industries= exposure to heavy metals like cadmium and nickel
- –Painters & furniture makers= solvents/ preservatives (cancer of sinonasal cavities and paranasal sinuses)
What are the target tissues of the following agents:
a) aflatoxin
b) asbestos
c) X-rays
d) Hep B virus
e) HPV (human papilloma virus)
a) Liver
b) Lung Pleura
c) Bone marrow (leukaemia)
d) Liver
e) Cervix
What 2 things do mutation induction (initiation) require?
1- Chemical modification of DNA
2- Replication of modified DNA and mis-incorporated by DNA polymerase
So need a PROMOTOR and INITIATOR
What are some mutations that can lead to a gain of function? (activation of proto-oncogenes)
Base pair substitutions
Amplification
Translocations
Inversions
What are some mutations that can lead to a loss of function? (inactivation of tumour suppressor genes)
Base pair substitutions Frameshifts Deletions Insertions Chromosomal rearrangements/ loss Promoter methylation
What is the most common Tumour Suppressor gene inactivation event?
Methylation of gene promotors (leading to epigenetic inactivation of TSGs)
What is benzopyrene?
(generated through combustion of meat, tobacco, fuel)
Example of a PRO-CARCINOGEN that requires metabolic activation before it becomes able to react with DNA. (to become BPDE)
What is Ataxia Telangiectasia (A-T)
Inherited defects in the ATM gene give rise to this, they have an elevated incidence of cancers:
- abnormal sensitivity of A-T cells to x-rays)
- ATM gene product interacts with the products of tumour suppressor genes (TP53 and BRCA1)
What is Lynch Syndrome (HNPCC- Hereditary non-polyposis colorectal cancer)?
Autosomal dominant disorder caused by a mutation in a mismatch-repair gene (MSH2, MSH6, PMS1 etc etc) Confers risk of developing colorectal cancer (also cancers of the endometrium, stomach, SI, liver and biliary tract, etc)
What is Xeroderma Pigmentosum (XP)?
(Inherited defects in the NER repair pathway) –> a group of rare autosomal-recessive inherited disorders characterised by extreme skin sensitivity to UV light, abnormal skin pigmentation, and high frequency of skin cancers.
What are some defence mechanisms against Carcinogenesis?
- Dietary antioxidants
- Detoxification mechanisms
- DNA repair enzymes
- Apoptotic response to unrepaired genetic damage
What are some of the risk factors for breast cancer?
(all associated with increased exposure to estrogen which can both stimulate cell division and induce DNA damage)
- Alcohol consumption
- Oral contraception
- Hormone replacement therapy
- Late age of 1st pregnancy
- Early menarche
- Late menopause
Why is chronic inflammation associated with many types of cancer?
1) DNA damage from release of free radicals by immune cells (INITIATION)
2) Growth factor induced cell division to repair tissue damage (PROMOTION)
3) Tumour Associated Macrophages (TAMs) from inflammation are recruited (by cytokines released from tumour cells) and produce TNF-alpha (induces and maintains inflam response)
What are ROS and RNS?
Reactive oxygen species also released by Tumour associated macrophages (TAMs), that can act as complete carcinogens (so damage DNA and stimulate proliferation through induction of growth factors)
What are the 4 stages in the mechanisms of Oncogene Activation?
1- TRANSLOCATION of an oncogene from a low to an active transcriptional site
2- POINT MUTATION - substitution of a single base produces a hyperactive oncoprotein
3- AMPLIFICATION by insertion of multiple copies of an oncogene (increased expression)
4- INSERTION of a promotor or enhancing gene (by retroviruses) near an oncogene= increased expression
What are some functions of oncoproteins?
- Growth factor receptor that activates cell growth eg)HER2 amplification
- Binds DNA to stimulate transcription & expression of other genes.
- Activates signalling for cell cycle progression & cell growth
What are antioncogenes and gatekeepers?
Antioncogenes/ gatekeepers are negative regulators of the cell cycle & proliferation, and positive regulators of apoptosis.
Caretakers maintain genetic stability.
What is epigenetic silencing?
Shutdown of gene expression via methylation of CpG sequences in promotor regions.
What type of mutations occur in Tumour Suppressor Genes?
Recessive (so both copies of TSGs have to be mutated or epigenetically inactivated for complete loss of function)
(TSGs and Familial Cancer Syndrome…)
What gene causes Retinoblastoma?
RB1
(TSGs and Familial Cancer Syndrome…)
What gene causes Li-Fraumeni syndrome?
p53 (sarcoma, breast)
(TSGs and Familial Cancer Syndrome…)
What gene causes Familial adenomatous polyposis?
APC (colorectal)
(TSGs and Familial Cancer Syndrome…)
What genes are associated with Familial breast cancer?
BRCA1, BRCA2 (caretakers)
(TSGs and Familial Cancer Syndrome…)
What genes are associated with Hereditary Non-polyposis colorectal cancer? (lynch)
hMLH1, hMSH2 (caretakers)
What are the 7 hallmarks of Cancer Cells?
1) Self-sufficiency in growth signals
2) Insensitivity to antigrowth signals
3) Tissue invasion and metastasis
4) Limitless potential for replication
5) Sustained angiogenesis
6) Evading apoptosis
7) Genomic Instability
What may EGFR overexpression cause?
- Colorectal cancer
- Pancreatic cancer
- Lung cancer
- Non small cell lung cancer
What may a Ras mutation cause?
- Pancreatic cancer
- Papillary thyroid cancer
- Colon cancer
- Non small cell lung cancer
What may a B-Raf mutation cause?
- Melanoma
- Papillary thyroid cancer
- Colon cancer
What is E-cadherin?
Epithelial cells are held tightly together by adhesion molecule E-cadherin.
Many tumours show loss of E-cadherin through mutation/hypermethylation of the gene.
This results in epithelial-mesenchymal transition (EMT)
(TNM) What does T stand for and mean?
T0= extent of primary tumour.
T1-T4: increasing size/ local invasion of tumour.
(TNM) What does N stand for and mean?
N0= extent of regional (local) Nodal metastases.
N1-3: Increasing involvement of regional lymph nodes.
(TNM) What does M stand for and mean?
M0= No distant Metastases M1= Distant Metastases identified
Difference between well and poorly differentiated tumours?
Well differentiated tumours= slower growing and spread at a slower rate.
Poorly differentiated tumours= fast growing and more likely to spread and metastasise.
