Oncology: Principles Flashcards
What are the most common cancers in dogs?
Lymphoma Leukaemia Mammary cancer Osteosarcoma Oral melanoma Mast cell tumours Prostate cancer Brain cancer
Most cancers are …….clonal
Poly
What are the two types of mutation that can cause cancer?
Point mutations: a change to one or a few of the bases in the DNA sequence
Chromosomal alterations: a change in the number or composition of the chromosomes
What happens to the DNA methylation and histones in cancer?
They are modified
What are the hallmarks of a cancer cell?
Self sufficiency in growth signals Insensitivity to anti-growth signals Limitless replicative potential Evading apoptosis Sustained angiogenesis Tissue invasion and metastasis
What are oncogenes?
Genes that promote cell proliferation
What are tumour supressor genes?
Genes that prevent aberrant cell proliferation
What are proto-oncogenes?
Viruses have genes that promote cancer (Oncogene: v-Src, protein tyrosine kinase)
Mammalian cells have equivalent genes (C-src) but the are normally regulated, so do not promote cancer
These genes are called proto-oncogenes (c-Src)
How do cancer cells look different on cytology?
Large nucleus
Cell becomes less specialised for function
Necrosis
A high mitotic index (How many metaphase cells there are)
What is the difference between the differentiation of benign and malignant cancers?
Benign:Well differentiated, similar to surrounding tissue, little or no anaplasia
Malignant:Lack of differentiation, atypical structure, variable anaplasia
What is the difference between the growth rate of benign and malignant cancers?
Benign: Slow or progressive, rare/normal mitotic figures
Malignant: Slow to rapid growth, Many/abnormal mitotic figures
What is the difference between the local invasion of benign and malignant cancers?
Benign: No invasion, cohesive growth, capsule often present
Malignant:local invasion, infiltrative growth, usually no capsule
What is the difference between the metastasis of benign and malignant cancers?
Benign: None
Malignant: Frequent
What is the difference between the host consequences of benign and malignant cancers?
Benign: Space occupying mass
Malignant: Life threatening
What is the difference between the host consequences of benign and malignant cancers?
Benign: Space occupying mass
Malignant: Life threatening
What are the characteristics of malignant cancer tissue?
Disorganisation of the tissue Increased nuclear or cell pleomorphism Large and/or multiple nuclei Increased amount of necrosis High cellularity and minimal stroma
Scirrhous or desmoplastic reaction: cancer cells secrete a lot of cytokines to the stroma and the stroma reacts with inflammation
What do you call a benign tumour of the fibrous connective tissue?
fibroma
What do you call a benign tumour of the fat?
Lipoma
What do you call a benign tumour of the glandular epithelium?
Adenoma
What do you call a benign tumour of the protective epithelium?
Papilloma
What do you call a benign tumour of the CNS astrocytes?
Astrocytoma
What do you call a malignant tumour of the fibrous connective tissue?
Fibroscarcoma
What do you call a malignant tumour of the fat?
Liposarcoma
What do you call a malignant tumour of the glandular epithelium?
Adenocarcinoma
What do you call a malignant tumour of the protective epithelium?
Carcinoma
What system do we use to grade tumours?
TMN system :
Size of primary tumour (T)
Degree of lymph node involvement (N)
Extent of metastasis (M)
How do we grade the N by the TNM system?
N0- no LN involvement
N1 - local
N2 - Distant
How do we grade the M by the TNM system?
M0: No detectable metastasis
M1: Metastasis
How are metastasis formed?
Metastases are formed by cancer cells that have left the primary tumour and travelled through blood and lymphatic vessels
Are melanomas highly metastatic?
Yes
Are squamous cell carcinomas highly metastatic?
No
Is metastasis related to tumour size?
Not necessarily, but larger tumours will have more cells to shed
What is the theory of how metastasis seeds form?
Dissemination starts early (1-4mm)
Different organs seeded in parallel – not sequentially
Growth of disseminated tumour cells may need extra factors produced by the primary tumour or micro-environment
What are the stages in metastasis?
- Invasion and intravasion
- Epithelial to mesenchymal transition (EMT)
- Intravasion stimulated by tumour associated macrophages (TAM)
- Transport and extravasion
- Colonisation
How does invasion and intravasion of metastasis occur?
Intravasion: Breakdown of the basement membrane by secretion of matrix metalloproteinases (MMPs) which degrade components of the ECM
Cell become highly invasive through a process that changes their phenotype from epithelial to mesenchymal, what causes EMT?
EMT stimulated by factors secreted by the stroma (e.g. TGFβ, TNFα)
What does EMT allow and how does it occur?
EMT enables cells to acquire invasiveness, motility and a heightened resistance to apoptosis
Epithelial markers are down-regulated and mesenchymal markers are up-regulated eg. Loss of E-cadherin (gain of A-cadherin which allows the cancer cell to escapr from its partners and change into the stroma) and acquisition of vimentin
What are the two strategies of extravasion?
Rapid (mins): trigger endothelial cell of vessel wall to retract leaving space for extravasation
Slow (days): requires proliferation and subsequent destruction of the parenchyma
After extravasion what happens to the tumour cell?
EMT reverts to MET
Colonisation – expansion into macroscopic masses (>2mm diameter)
What are transcoelomic tumours?
Cancers that arise on the surface of abdominal and thoracic structures (mesotheliomas, ovarian adenocarcinomas)
What happens to the LN closes to the tumour?
Lymph node closest to the tumour are colonised earliest and develop the largest tumour masses (adenocarcinoma of intestine metastasise to the mesenteric lymph node and other of the abdominal cavity)
What is the haematogenous pathway of metastasis?
Travelling via the blood, tumours generally invade veins other than arteries (ultimately entering in the lungs and liver)
Sarcomas tend to use this path more frequently than carcinomas.
What primary tumours like to metastasise to the lung?
– Osteosarcoma
– Haemangiosarcoma
– Melanoma
– Mammary tumours
What primary tumours like to metastasise to the lung?
Osteosarcoma
Haemangiosarcoma
Melanoma
Mammary tumours
What primary tumours like to metastasise to the liver, spleen and/or kidney?
Mast cell tumours
Haemangiosarcoma
What primary tumours like to metastasise to the bone?
Mammary
Prostate
Bladder
In metastasised bone tumours how to the cancer cells reach the bone? What attracts them there?
via the vessels of the bone marrow
They adhere to the specialised stromal cells coating the bone facing the marrow.
They are attracted by growth factors contained in the ECM (organic scaffolding of the bone)
When cancer cells metastasise into the bone what do they do?
Cancer cells activate osteoclasts and osteoblasts at different extents resulting in GF’s causing osteolytic and osteoblastic metastasis
How are occult micrometastasies kept alive?
Cellular dormancy/quiescence or Tumour mass dormancy (TMD)
TMD is thought to be by Angiogenic restriction or kept in check by Immune surveillance
Not proliferating or proliferating slowly is a good evasion tactic for cancer drugs which target replicating cells
