Introduction to Tumour Biology Flashcards
Differentiation in the Embryo
Early cells identical
Cells become different from one another
-ectoderm, mesoderm, endoderm
Cells also differentiate within each layer
Post embryonic Differentiation
Occurs at the level of cells rather than whole tissues
Maturation of Differentiated cells from (basal) Proliferating cells
-mitotic activity gradually migrating to surface, differentiating as they move up producing keratin, forming flakey layer and terminating proliferation genes
Differentiation involves:
Inactivation fo Proliferation genes
-Activation of specific Function genes
De-differentiation involves:
Involves reversion to Primitive, embryonic, proliferative phenotype as occurs in neoplasia
-when things go wrong
-not the mature cells,
-is more the proliferating cells, instead of maturating, continue proliferating and forming abnormal tissues that are incompletely differentiated and have excess proliferative activity
-“neoplasia” = new growth
“tumour”= swelling
Disorders of Growth
Disorders in the regulation of cell proliferation or differentiation
- Embryo - malformation
- Post-natal
- Abnormalities of Tissue function
- Abnormalities of Tissue Mass
Malformations
Caused by abnormality in growth and development in utero
- Haematoma= malformation of mature tissue
- e.g. “haematoma” in brain - arterial venous malformation –> can lead to hemoorahge/rupture
- Disorders in the regulation of cell proliferation or differentiation in the Embryo
Clinical Implications of disorders of Growth
- Not all are “disorders” - some normal (physiological) (callus thickening of skin in epidermis on hands with manual labour/hyperplasia)
- some have clinical consequences (ventricular hypertrophy –increased risk of myocardial infarct, decompensation and heart failure)
- some are reversible (cell enviro- hormones, irritation) (if stimulus removed tissue will return to normal state)
- others are irreversible (dysplasia, neoplasia- DNA change) (if cell divides changes are inherited by daughter cells)
Reduction in tissue mass
Agenesis/Aplasia: total absence
-e.g. one kidney doesnt develop
Hypoplasia: Congenital Reduction in size
-one kidney smaller than normal due to small number of callusies
Atrophy: Acquired reduction in size
-kidney w. poor blood supply due to atheromic plaque in renal artery –> shrinked/hypoplastic kidney (normal number of calluses)
-muscle in cast, less use, leads to atrophy
Change in Myocardium
all same magnification as nucleus size is the same
Atrophy: elderly or malnourished people. brown pigmenting
Hypertrophy: increased size of heart due to increase in size of heart muscle fibres. due to increased strain. e.g. due to increased systemic BP (hypertension)/ malfunctioning of valves in heart –> increased tendency to myocardial infarct –> dilation and failure
-Left Ventricular Hypertrophy
–> dilation
–> failure
Hypertrophy and Hyperplasia
Not neoplasia Hypertrophy=increased growth -organ and cells -e.g. only one kidney so enlarged -no relationship to cancer Hyperplasia= increased number of cells -relationship to cancer
Hyperplasia
Some examples are Premalignant (statistical/hyperplasia of uterus endometrium, rate of carcinoma of endometrium, discover risk)
Causes:
-“Functional” (Physiological) (thickening of epidremis in hands)
-Endocrine Stimulation (ovarian tumour produce estrogen causing hyperplasia (premalignant))
-Chronic Stimulation (ulcers thickening on edge)
Effects:
-Increased function (endocrine) (thyroid)
-Risk of Malignancy (some types)
Prostatic hyperplasia/Hypertrophy
Hyperplasia + Atrophy
Small Transition state of Prostate enlargens considerably
-hypertrophic/hyperplastic prostate
-hyperplasia increase in cell number occurs only in that cell
–not assoc. w increased carcinoma rate
–common but cancer risk is no larger compared to those with normal prostate
-simultaneously outer zone undergoes atrophy (thin epithelium lining glands)
Hyperplasia- Thyroid
Grave’s Disease= abnormal antibody
=autoimmune disease
TSH receptor= self
Hyperplastic
-stimulation of TSH receptor by autoantibody
-would do same if had tumour of pituitary to produce TSH
-same in Adrenal gland ACh inappropriately secreted –> hyperplasia of adrenal cortex
-histology: proliferation, cells chew up colloid , making into thyroid hormone –> hyperthyroidism
- density increases + gland expands
-gland becomes a visible palpable mass in the neck
= doesn’t predispose to malignancy
Which Hypertrophy/Hyperplasias result in predisposition of Malignancy?
Breast Hyperplastic changes
-accompanied by cystic change
-Endometrial changes in Uterus
=increased chance of cancer of those organs
Metaplasia
Some examples PRe Malignant
Change from one mature tissue type to another
Bronchus: normally only squamous as far as larynx, then respiratory epithelium in trachea/bronchus (which contain cilia)
-Smokers= irritation changes epithelium to squamous epithelium of throat/larynx
=premalignant change
=has to undergo additional change to undergo dysplasia - manifestation of premalignant features
Cervical metaplasia
Squamous metaplasia is normal
Endocervix (canal)= columnar epithelium
Squamous metaplasia
Ectocervix (vaginal) squamous epithelium
-occurs in every girl
-maturing to menarche, uterus grows and cervix changes in shape
-exposes thin glandular layer, upon exposure to different vaginal environment (from canal) changes to squamous epithelium
-can all look like vaginal ectocervical squamous epithelium - non keratinising squamous epithelium
-occurring in response to a stimulus
