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Summary SSA3 The nature of cancer
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Summary and WG answers of SSA3 The nature of cancer of the course MBO (molecular biology and oncology) at Leiden University.
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SSA3 The nature of cancerChapter 2 Weinberg
2.1 Tumors arise from normal tissue
Metastases can often be traced back to a primary tumor. Melanoma can spread to the lungs
and is easy to see because of the dark pigmentation. Colon cancer often metastasizes to the
liver via the portal vein. Tumor that grow locally without invading the adjacent tissue is a
benign tumor. Invasive and metastatic tumors are malignant. Most tumors are benign but can
still cause clinical problems because they can produce hormones (adenomas). Pituitary
adenomas can lead to acromegaly which is excessive growth due to production of GH.
2.2 Tumors arise from many specialized cell types
throughout the body
Epithelial cells are separated from the supporting stroma by the basement membrane (basal
lamina). The basement membrane has specialized ECM. Endothelial cells are special
epithelial cells. Epithelial cells are the derivative of the most common cancers, the
carcinomas (80% cancer related death). The epithelium if the lungs, liver, gallbladder,
pancreas, esophagus, stomach and intestine are all from the endoderm. The skin epithelium
is from the ectoderm. Ovaries are from the mesoderm.
Most carcinomas can be classified as squamous cell carcinoma or adenocarcinoma.
Squamous cell carcinomas are tumor that arise from epithelial cells that form a protective cell
layer. The adenocarcinomas secrete products and are often derived from luminar epithelium.
The first major class of nonepithelial cancer is from connective tissue (mesoderm) and are
the sarcomas but it is still only 1%. The
second major class are the hematopoietic
cancers. Leukamia refers to the
malignant derivatives of the white blood
cells. Lymphomas are specifically of the
B and T cells. These aggregate to form
solid tumors. The third class are the
neuroectodermal tumors which are all
named after their origin in the embryo.
Examples are gliomas, glioblastomas,
neuroblastomas, schwannomas and
medulloblastomas.
, A) Acute lymphocytic leukemia (ALL) is from B cells (80%) and T cells (20%). The cells have
markers of pre-B cells.
B) Acute myelogenous leukemia (AML) only have a little cytoplasm and a large nucleus.
They derive from precursors of granulocytes and monocytes.
C) Erythroleukemia consist of large erythroblasts that look like the precursors of the
erythrocytes.
D) Chronic myelogenous leukemia (CML) is of the myeloid lineage
E) Multiple myeloma (MM) is malignancy of the plasma cells and they secrete antibodies.
2.3 Some types of tumors do not fit into the major
classifications
Melanomas are from melanocytes which are derives from neural crest. They are present as
the pigmented cells in the skin and retina.
Small-cell lung carcinoma look like neurosecretory cells like in the adrenal glands. The
tumors originate from cells of the endoderm of the lung, but have epithelial characteristics
and of the neuroectodermal lineage.
The switch of tissue lineage to a new differentiated cell is transdifferentiation. The most
common form is the epithelial-mesenchymal transition (EMT).
Teratomas are very bizarre as they do not meet any of the normal classifications. They
areise from the germ cells that fail to migrate to their destination and therefore stay ectopic.
They still have their pluripotency. Often, all germ lines co-exist in one tumor which leads to
weird structures. What is remarkable, is that their genome is often still wild type.
Anaplastic tumors are dedifferentiated and you cannot use the histopathological criteria
anymore. It is impossible to see which tissue they are derived from. This is often called
cancer of unknown primary (CUP).
2.4 Cancers seem to develop progressively
Hyperplastic means that there is an excessive number of cells, but their appearance is still
quite normal. Metaplastic means that there is replacement of a cell type by another which is
not normally seen in that tissue. They look normal, but are just abnormal at that location. This
often occurs are epithelial transition zones and is often from squamous to mucus secreting.
This is also in Barrett's esophagus in which gastric secretory cells are now in the epithelium
of the esophagus. Dysplastic means that the tissue looks abnormal cytologically; the
appearance of the cell is not normal. There are cytological changes in for example the
nuclear size, shape, more staining etc. Dysplasia is considered the transition from benign to
premalignant.
More abnormal are the growths called adenomas, polyps, adenomatous polyps and
papilloma's. These are often large and dysplastic. Still, they often stop growing and a certain
point and do not cross the basement membrane boundary.
A further degree of abnormality is when there is invasiveness. Then it is called cancer.
Neoplasms are the collective name for benign and malignant tumors in which there is a new
type of tissue. Further abnormality is the metastasis.
Tumor progression: Normal Hyperplastic Dysplastic Neoplastic Metastatic
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