Lecture ILO’s Flashcards
Describe oncogenesis
The process of initiating and promoting the development of a neoplasm (or tumour) through the action of biological, chemical, or physical agents ie radiation, cariogenic agents.
Normal mucosa -> dysplastic mucosa -> adenocarcinoma
Classification of tumours
• Epithelial or carcinomas
• Non epithelial
• Unclassifiable
Epithelial tumours
• Epithelial tumours (or carcinomas) include cell types that arise from all three germ layers of the early embryo
Squamous cell carcinomas
from epithelial cells lining cavities or channels
Adenocarcinomas from specialised secreting cells within epithelia
Non epithelial tumours
Non-epithelial tumours derive from connective tissues originating from the mesoderm
– Sarcomas
Sarcomas are derived from mesenchymal cell types such as fibroblasts, adipocytes, osteoblasts, myocytes.
Ie osteosarcomas, liposarcoma
– Hematopoietic malignancies
Haematopoietic malignancies are those derived from the different cell types that constitute the blood. They can be subdivided in:
leukaemias (and erythroleukaemia): circulating malignant derivative of haematopoietic blood lineages
lymphomas: tumour of the lymphoid lineages that form solid masses, frequently in lymph nodes
Ie acute lymphocytic leukaemia, non Hodgkin’s lymphoma
– Neuroectodermal tumours
Neuroectodermal tumours originate from cells that form the various component of central and peripheral nervous system (gliomas, glioblastomas, neuroblastomas, schwannomas, and medulloblastomas).
– Teratomas/teratocarcinomas
Teratomas and their malignant counterpart teratocarcinomas originate from germ cells in ovaries and testis, respectively.
They contain a random selection of tissues including teeth and hair.
Melanoma
Melanomas derive from melanocytes, a cell type that arise in the neural crest and during development migrate to settle in the skin and eye to provide pigment but do not make direct connections with the nervous system
Easy to treat if surgically removed if caught early before invading subcutaneous tissue
Small cell lung carcinoma
Small cell lung carcinoma
• The most common form of lung cancer in smokers.
• Cells have neurosecretory activity but they probably originate from endodermal cells of the lung that have lost their epithelial characteristic and taken that of neuroectodermal cells (transdifferentiation)
Anaplastic tumours
Anaplastic tumours
• Anaplastic tumours consist of cells that have dedifferentiated to an extent that it is no longer possible to identify the tissue from which they have arisen.
• These tumours represent 1-2% of samples given to pathologists for analysis.
Hyperplasia
Cells have normal appearance, but are excessive in number
Right cells, in the right place, just too many of them
Metaplasia
Normal cell types displaced by another, still normal in appearance, but not normally encountered at the specific location.
• Frequently observed in epithelial transition zones (e.g. cervix/uterus or oespohagus/stomach), where a squamous epithelium normally undergoes an abrupt transition into a mucus-secreting epithelium.
Ie Barrett’s oesophagus
Dysplasia
Cells are cytologically abnormal
– Variability in nuclear size and shape
– Increased nuclear staining (by dyes)
– Increased ratio of nuclear vs cytoplasmic size
– Increased mitotic activity
– Lack of cytoplasmic features associated with the normal tissue cells
Adenomas
Adenomas (aka polyps, adenomatous polyps, papillomas, and, in skin, warts - benign tumours) are large growths that can be readily detected with the naked eye
– They contain all the cell types of the normal tissue but have undergone a substantial expansion, giving the tissue a dysplastic appearance
– They usually grow to a certain size and then stop and do not invade the basement membrane
Neoplasia
Invasive growths (or neoplasia) are malignant tumours that have acquired the ability to brake the basement membrane and invade the surrounding tissue.
– Epithelial cells must undergo the epithelia-mesenchymal transition (EMT) to be able to invade adjacent tissue
Spread to cells with similar surface receptors
Metastasis
• Metastases (aka ‘mets’) are secondary tumours that form at distant sites from founder cells (those that have left the primary tumour).
• They account for 90% of cancer death
• The process of metastasis depends on the ability of cancer cells to:
– invade adjacent tissue
– enter blood and lymph vessels
– Invade underlying tissue
– Found a new tumour cell colony at the distant site
Tumour suppressor genes
Stop cells from dividing out of control by producing very specific protein regulators to stop proliferation
Oncogenes
Genes which stop slowing the cell cycle
• Oncogene: a cancer-inducing gene, or a gene that can transform cells.
• Closely related, or identical to a normal gene or “proto- oncogene”, a gene likely to be involved in essential functions of the cell related to control of proliferation and differentiation.
• Cells are stimulated by growth factors, which bind to cell surface receptors, activating intracellular signalling pathways, leading to alterations in gene expression. Proto-oncogenes function at each of these steps. Mutations in any of these genes can give rise to oncogenes, whose products promote cell growth in the absence of external stimuli.
