Tumour Pathology 2 Flashcards
What is the affect of the loss of tumour suppressor genes?
Allows cancer to develop due to uncontrolled cell proliferation
Three examples of tumour suppressor genes
- Adenomatous polyposis (APC) - colon cancer
- Retinoblastoma (Rb)
- BRCA1 - breast cancer
What is the affect of gain of function of oncogenes?
Develops cancer as it is mutated proto-oncogene and allows cell to continually proliferate uncontrollably
Examples of oncogenes
- B-raf
- cyclin D1
- ErbB2
Properties of cancer cells
- Altered cellular function
- Abnormal morphology
- Cells capable on independent growth
- Tumour biomarkers
Describe the altered cell functions of cancer cells
- Loss of cell-cell adhesion
- Loss of cell-matrix adhesion - allowing spread of tumour cells
- Production of tumour biomarkers
Describe Tumour Biomarkers
Indicate presence of cancer
- onco-fetal proteins
- expressed in fetal tissue
- oncogenes
- growth factors & receptors
Clinical use of tumour biomarkers
- Screening: look for cancer in those susceptible
- Diagnosis: symptoms & signs lead to type of cancer
- Prognosis: identifying patients with specific outcome
- Predictive: identifying patients who will respond to therapy
Tumour biomarker for colorectal cancer
- Kras (oncogene)
- Carcino-embryonic antigen (CEA)
Tumour biomarker for Lung cancer
- EGFR (growth factor)
- PD-L1 (immune checkpoint inhibitor)
Tumour biomarker for Melanoma
Braf (oncogene)
Tumour biomarker for breasT cancer
- Her2-GF
- Oestrogen receptor
Tumour biomarker for prostate cancer
Prostate specific antigen
Describe morphology of cancer cells
-Cellular and nuclear pleomorphism (variation in size and shape)
Characteristic of tumour growth
It is a balance between cell growth and cell death - angiogenesis and apoptosis
What is angiogenesis?
- New blood vessel formation which sustains tumour growth
- Provides route for release of tumour cells into circulation - metastases
What is apoptosis?
- Programmed cell death
- Regulates tumour growth
- Responds to chemotherapy and radiotherapy
Clinical significance of metastases
- Problem due to formation of metastatic (secondary) tumours from spread from primary sites
- Prognosis depends on extent of cancer spread
Mechanism of invasion and metastasis
- Matrix degradation by proteolytic enzymes - breakdown of connective tissue around cancer = spread
- Less cell-cell and cell-matrix adhesion allowing for spread
- Increased adhesion for colonisation
Modes of spread of cancer
- Local spread - invades surrounding structures
- Lymphatic spread
- Blood spread
- Transcoelomic spread - special form of local spread
Steps in tumour invasion
- Malignant tumour
- Invasion into connective tissue
- Invasion into lymph/blood vessel
Invasion via lymphatics stages
- Tumour cells adhere to lymph vessels
- Invasion into lymphatics and then to lymph nodes
- Colonisation in lymph node
Invasion via blood stages
- Tumour cells adhere to blood vessels
- Invasion into blood and then to tissue
- Colonisation
Describe trans-coelomic spread
- Spread of tumour cells across body cavities
- Tumours of lung, stomach, colon and ovary
Common sites of metastases
- Liver
- Lung
- Brain
- Bone (axial)
- Adrenal gland
- Omentum
Uncommon sites of metastases
- Spleen
- Kidney
- Skeletal muscles
- Heart
What tumours normally metastasise to bone tissue?
Breast and prostate
What tissue does colorectal cancer metastasise to?
Liver
What tissue does ovarian cancer metastasise to?
Momentum
