Tumour pathology 2 Flashcards
Properties of cancer cells
- Loss of tumour suppressor genes
- Gain of function of oncogenes
- altered cellular function
- abnormal morphology
- cells capable of independent growth
- BUT no single feature is unique to cancer cells
- tumour biomarkers
Tumour suppressor genes?
‘suppress tumour development’ normally act to inhibit cell proliferation and prevent tumor development
switched off in tumours
What is an oncogene? Gain of function of oncogenes?
a gene which in certain circumstances can transform a cell into a tumour cell. Expressed (turned on) transform into tumour e.g
B-raf
Cyclin D1 etc
‘Loss of cellular function’ expand
loss of cell-to-cell adhesion- cells don’t stick together
altered cell-to-matrix adhesion- cells don’t stick to underlying connective tissue (matrix)
production of tumour-related proteins- tumour biomarkers
Tumour biomarkers?
substance or process that is indicative of the presence of cancer in the body
may be produced by the cancer tissue itself or by other cells in the body in response to cancer
groups of proteins, maybe genes
-many different potential markers of cancer development and progression
can be used diagnostically/therapeutically
Clinical utility of tumour biomarkers
screening
diagnosis
prognostic- identifying patients with a specific outcome
predictive- identifying patients with tumour with specific properties that would benefit from administration of specific drug/therapy
Clinical use of oestrogen receptor?
Breast cancer
Clinical use of Carcino-embryonic antigen (CEA)?
CEA is a blood test used to help diagnose and manage certain types of cancers. The CEA test is used especially for cancers of the large intestine and rectum.
i.e Colorectal cancer
What is the BRAF biomarker? and which cancer is it useful for detecting/managing?
BRAF is a gene (oncogene)
many mutations of the BRAF gene have been found at a high frequency in specific cancers
testing for BRAF mutations is useful for Melanoma detection and management
What is tumour growth a balance between?
is balance between cell growth (angiogenesis) and cell death (apoptosis)
Tumour angiogenesis
New blood vessel formation by tumours
required to sustain tumour growth- the more blood vessels in and around the tumour means the worse the cancer outcome as there is more chance of it spreading by breaking off and moving into circulation
provides route for release of tumour cells into circulation
Apoptosis
Programmed single cell death
active cell process
regulates tumour growth- have apoptosis as cancer doesn’t take over whole body- it’s a balance
over proliferation- results in cancer
involved in response to chemo or radiotherapy
Why is the spread of cancer significant clinically?
prognosis depends on extent of cancer spread
if metastatic tumours form this is a major clinical problem
What is the simple 3 step process of tumour spread?
normal
tumour
metastasis
in reality- not this linear
What are some modes of spread of cancer
local spread
lymphatic spread
blood spread
trans-coelomic spread
Trans-coelomic spread?
Special form of local spread
spreading across a body cavity, such as through the pleural, pericardial, or peritoneal cavity.
tumours of lung, stomach, colon and ovary show this spread
Tumour metastasis via blood
- adherence of tumour cells to blood vessels
- invasion from blood vessels
- invasion into tissue
- formation of metastasis
- clinical evidence of metastasis
Tumour metastasis via lymphatics
adherence of tumour cells to lymph vessels
- invasion from lymphatics
- invasion into lymph node
- formation of metastasis in lymph node
- clinical evidence of metastsis
Common sites of metastasis
liver lung brain bone- axial skeleton adrenal gland omentum/ peritoneum (abdomen membrane)
Uncommon sites of metastasis
spleen
kidney
skeletal muscle
heart
What is a tumour marker?
Tumour markers are substances that are produced by cancer or by other cells of the body in response to cancer or certain benign (noncancerous) conditions.
Most tumour markers are made by normal cells as well as by cancer cells; however, they are produced at much higher levels in cancerous conditions.
Can be found in the blood, urine, stool, tumour tissue, or other tissues or bodily fluids of some patients with cancer. Most tumour markers are proteins.
Issues with tumour markers?
- non-cancerous conditions can cause the levels of certain tumour markers to increase
- not everyone with a particular type of cancer will have a higher level of a tumour marker associated with that cancer
- tumour markers have not been identified for every type of cancer
How are tumour markers used in cancer care?
help detect, diagnose, and manage some types of cancer
Tumour marker levels may be measured before treatment to help doctors plan the appropriate therapy
Tumour markers being used throughout treatment help to do what?
Tumour markers may also be measured periodically during cancer therapy. A decrease in the level of a tumour marker or a return to the marker’s normal level may indicate that the cancer is responding to treatment, whereas no change or an increase may indicate that the cancer is not responding.
Tumour markers may also be measured after treatment to check for what
to check for recurrence
Define ‘pleomorphism’
vary in size and shape
Examples of tumour suppressor genes
Adenomatous polyposis (APC)
Retinoblastoma (Rb)
BRCA1
General main classes of tumour biomarkers
onco-fetal proteins, oncogenes, growth factors and receptors, immune checkpoint inhibitors
Onco-fetal proteins
expressed normally in fetal tissues. Switched off in post-fetal life but switched back on in tumours
Alpha-fetoprotein
one of the main proteins expressed in fetal liver
expression is switched off in post-fetal life. Good for identifying malignant testicular teratoma and hepatocellular carcinoma (malignant)
Carcino-embryonic antigen (CEA)
indicator of colorectal cancer
CEA is switched off post-natal life then switched back on in tumours
Use this marker to monitor response/progression of tumour after treatment
Receptors that can detect breast cancer?
Breast cancer cells often have receptors (proteins) that hormones or other proteins can attach to and stimulate the cancer to grow
Oestrogen receptor:- Breast cancers with receptors for the hormone oestrogen
Some breast cancers have high numbers of receptors for the protein HER2 (human epidermal growth factor
Prostate specific antigen biomarker?
Useful in terms of possible diagnosing but certainly monitoring therapy and progression of prostate cancer.
Commonly used clinical bio-marker
Kras is a useful biomarker to predict which tumour?
colorectal cancer
Braf is a useful biomarker to predict which tumour?
melanoma
EGFR (epidermal growth factor receptor) is a useful biomarker to predict which tumour?
renal cancer
PD-L1 is a useful biomarker to predict which tumour?
lung cancer
Her 2 is a useful biomarker to predict which tumour?
Breast and gastric cancer
Her2 is part of the EGFR family
Herceptin is used to select patients for herceptin treatment for breast cancer and gastric. The drug binds to Her2 molecule (it is a receptor)
pleomorphism?
Varying in size and shape
Clinical evidence of metastasis in lymphatics
imaging
feeling of large lymph nodes
histology- most sensitive way
