Cancer Genomics An introduction - Week 10 Flashcards
Statistics
Cancer is the second leading cause of death in the world
Testicular cancer – 98% of patients survive 10 years or more
Pancreatic cancer – only 1% of patients survive 10 years or more
What is Cancer
Uncontrollable cell division where the abnormally dividing cells eventually spread to or invade other tissues – metastasis which could lead to the death of a patient
Cell division - mitosis
Cell reproduce by cell division (mitosis)
1 cell becomes 2, 2 cells become 4, 4 cells become 8 etc
• Mechanism for making new body cell and is distinct from meiosis (making egg and sperm cells – not covered in this module)
• The cell cycle is the whole series of changes the cell goes through from the time it is first formed until it divides into two daughter cells starting and ending with mitosis
In normal healthy tissue the progression through cell division/ cell cycle is
tightly regulated and only occurs when needed stimulated by cell signalling pathways
Cancer Terminology
Cancer or neoplasia (neo – new, plasia – tissue/cell) or malignant tumour
Tumour
swelling or mass
tumour in the context of cancer
referring to a mass of non structured new cells with no known purpose in the physiological function of the body
Benign - differentiation
Well differentiated, structure similar to tissue of origin (more likely to retain some of the function of their cell of origin
Benign - rate of growth
Slow growing and may halt or regress
Benign - local invasion
Usually cohesive and well defined (capsular), does not invade or infiltrate into other tissues (relatively innocent)
Benign - metastasis
Absent (do not spread to other sites in the body
Malignant - differentiation
Poorly differentiated (or completely undifferentiated or anaplastic)
Malignant - rate of growth
Erratic but can be fast (faster than benign)
Malignant - local invasion
Locally invasive and infiltrates surrounding tissue (invade and destroy adjacent structures and spread/metastasise to different sites in the body)
Malignant - metastasis
Frequent but more likely with large undifferentiated tumours
• Benign tumours
In general have the suffix OMA attached to the name of the cell type the tumour originates
Fibroma (fibrous tissue benign neoplasm)
Adenoma (Epithelial benign neoplasm)
Malignant tumours
Similar nomenclature as benign tumours (with additions)
Fibrosarcoma
Adenocarcinoma
Liver =
Hepatic adenoma (benign) or hepatocellular carcinoma (malignant)
Metastasis
(characteristic that differentiates benign and malignant tumours)
• Spread of a tumour to sites that are physically discontinuous from the primary tumour. Metastatic spread of a tumour decreases the possibility of a cure so understanding metastatic spread is critical especially when approximately 30% of newly diagnosed solid tumours present with metastases.
Depending on how lymph and blood travel through the body Primary tumours often have a preferred site of metastasis
in addition to the lymph nodes i.e. tumours of bladder, breast, colon and ovary
From these examples you can see that bone, liver and lung are common sites of metastasis
Three main pathways that a tumour can spread to distant sites
Seeding of body cavities and surfaces (can occur when a malignant tumour penetrates into an open field such as the peritoneal cavity in ovarian cancer, spread through
Lymphatic spread of cancer cells (spread through the lymphatic system is the most common pathway for the initial dissemination of carcinomas while tumours do not contain functional lymphatic vessels, it appears that the vessels at the edges of tumours are sufficient for lymphatic spread.)
Hematogenous spread (blood vessels) (tumours can also spread through nearby blood vessels either through veins (more common) and arteries (less common as arteries are thicker, more muscular and harder for tumour cells to penetrate)
Metastasis are a multiple step process and involve
growing into or invading nearby tissue, moving through the walls of nearby lymph or blood vessels, travelling through the lymphatic/blood stream to other parts of the body. Stopping in small blood vessels at a distant location then managing to invade these blood vessels and moving into surrounding tissue, ultimately growing into a tiny tumour which develops blood vessels which will allow it to keep growing to a larger size.
To undergo these metastatic step processes,
tumour cells have to acquire a number of different characteristics. Similarly normal cell to become a tumour cell initially the normal cell needs to acquire a number of different characteristics
Collectively these characteristics are defined as the
“hallmarks of cancer” and were first defined by Hanahan and Weinberg in 2000
To help inform treatment decisions and inform patients of their prognosis, cancers are examined to determine
stage and grade:
grade
histological assessment of state of differentiation
differentiation of low grade tumours
generally well differentiated
differentiation of high grade tumours
poorly differentiated or completely undifferentiated
Grade X
Grade isn’t known
Grade 1
Well differentiated, low grade
Grade 2
Moderately differentiated, intermediate grade
Grade 3:
Poorly differentiated, high grade
Grade 4:
Undifferentiated, high grade
Grading used for most tumours except for some exceptions i.e.
o Gleason score for prostate cancer
o Nottingham score for prostate cancer
Stage
looking at the size and spread of the tumour
Solid tumours TNM system (most common system)
T = Primary tumour (size, invasive depth and infiltration)
N = Involvement of the lymph nodes (number of lymph nodes)
M = Distant metastases (have distant metastases been observed)
Each tumour type has its own and often complex staging system based on these principles but there are 2 main systems :
Union of Internal Cancer Control (UICC)
• Aims to be more succinct, meets the needs of the worldwide community and used in the UK
American Joint Committee on Cancer (AJCC)
• Aims to be comprehensive and meet the needs of US academics
Both systems are very similar
