Module 35 - Neoplasia Flashcards
Mutations in cancer stem cells or progenitors would lead to ________________.
Cancer Heterogeneity
How does selective pressure and clonal evolution leads to tumour progression?
Tumour progression involves successive rounds of mutation (generates diversity), accumulating somatic mutations in the process.
Natural selection (selective advantage) will enrich subclones with ability to thrive in the environment, with well-adapted cells becoming the dominant clone.
Mention what factors affect cancer clonal evolution.
- mutation rate
- number of cells in the population
- rate of proliferation of mutant cells
Describe the mechanism of invasion/migration of cancer cells.
It involves the following steps:
- Detachment of cancer cells from each other - reduced expression of cadherin (EMT)
- Attachment to extracellular matrix component - an expression of receptors for fibronectin, laminin, collagen
- Degradation of ECM - cancer cells secrete proteolytic enzymes or induce host cells to produce proteases, e.g. cathepsin D, metalloproteinases
Describe the mechanism of metastasis of cancer cells.
To establish a distant metastasis a cancer must contain cells which have accumulated genetic/epigenetic changes to enable them to :
- Detach from their anchor - adhesion molecules
- Invade local blood/lymph vessels - proteolytic enzymes
- Evade the immune system - tumour immunology
- Colonise tissue at distant site - environment, GF
- Establish a nutrient supply (angiogenesis)
Describe the Linear Progression Model.
It refers to the accumulation of genetic and epigenetic changes leading to increased severity of the disease.
For example, the progression of colorectal cancer is typically very slow (10-35 years in which tumour detectable, but not malignant). Metastasis initiated during late stages of the primary tumour.
Compare between the LInear and Parallel Progression Model
in the linear progression model , late stage tumour cells disseminate and form metastases. In contrast, in the parallel progression model , early tumour cells disseminate and form metastases alongside the primary tumour, and both primary tumour and metastases progress in parallel gaining multiple subclonal populations
Describe the Parallel Progression Model with examples.
In PPM, metastasis is initiated before symptoms appeared or primary tumour is diagnosed. Early adaptation and dissemination of cancer cells leading to the metastases to have different genomes from the primary tumours.
For example, in the case of breast cancer, multiple metastases arise from the primary tumour. Each tumour site progress in parallel at different rates in different organs. This results in the diverse genetic/epigenetic alterations of the sites.
Note: factors secreted by the primary tumour may stimulate colonisation in the first place
Mention the aetiology of cancer.
Genetic, environmental, chance
Define neoplasia.
A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissue in the same manner after cessation of the stimuli which evoked the change.
Differ between benign and malignant neoplasms.
Benign neoplasms:
- Lack of capacity to invade local tissue
- Localised to their site of origin
- Well-differentiated (similar to tissue of origin)
- Discrete, palpable, and mobile
Malignant neoplasms:
- ability to invade and replace local normal tissue
- potential to metastasise
- less differentiated
- difficult to resect by surgery
Define and describe anaplasia.
It’s a condition of cells with poor cellular differentiation, losing the morphological characteristics of mature cells and their orientation with respect to each other and to endothelial cells.
Morphology includes:
- polymorphic - variation in size and shape
- hyperchromatic nuclei
- frequent mitosis
- loss of polarity (disorganised growth)
- ischemic necrosis (due to rapid growth - insufficient blood supply)
Define aplasia, agenesis, hypoplasia, dysplasia.
Aplasia: failure of organ or tissue to develop or function normally
Agenesis: the complete failure of development of organs
Hypoplasia: partial failure of development, the organ doesn’t develop to normal size
Dysplasia: abnormal cells, pre-malignant condition of cell-proliferation
Describe Kaposi’s Sarcoma.
It is caused by HHV8 in an immunocompromised person (due to HIV/AIDS). It is a disease of the vasculature - where the virus-transformed endothelial cells lead to the extravasation of RBCs into the dermis.
This is diagnosed physically as pink-red to purple macules, papules, plaques, or nodules.
Explain how HHV8 contribute to the development of Kaposi’s Sarcoma.
Growth of sarcoma requires viral IL-6 produced by HHV8, which induces angiogenesis and inflammation.
The angiogenesis process is defective leading to leaky blood vessels and the extravasation of RBCs to the dermis.
Describe how you grade cancer.
It is based on the degree of differentiation of the tumour cells, the number of mitoses and architectural features. Typically classified into low and high grades.
