Unit 1- The Nature and Hallmarks of Cancer Flashcards
What is cancer?
- group of diseases that originate from a LOSS OF CONTROL of cell division/ differentiation/ survival/ death mechanisms
What is the loss of cellular control in cancer a result of?
Mutations = dynamic changes in cell genome
What results in the uncontrollable proliferation of cells into a mass? (tumor)
- mutation (changes in cell genome) in cooperation with a permissive microenvironment
Do all cancers form a tumor mass?
No- ex) leukemia
What are the hallmarks of cancer?
- Sustaining proliferative signaling
- Evading growth suppressors
- Avoiding immune destruction
- Enabling replicative immortality
- Tumor-promoting inflammation
- Activating invasion/ metastasis
- Inducing angiogenesis
- Genome instability/ mutation
- Resisting cell death
- Deregulating cellular energetics
What is the first report of cancer?
- reported in the Smith Papyrus > bulging mass under breast
- Imhotep, an Egyptian physician
What was the first “true” evidence of cancer in humans?
- Osteosarcoma in mummy from the Atacama desert
What is the oldest case of cancer?
- Osteosarcoma in leg of 76 million yrs old dinosaur fossil in Alberta
What is the origin of the term carcinoma?
- first used by Hippocrates to describe solid tumors
- based on way blood vessels organized around tumors like a crab
What does the term carcinoma currently denote?
- malignant solid tumors of epithelial origin only
What is the difference between cancer/ carcinoma?
Cancer- malignant tumors of all types
Carcinoma- malignant solid tumors of epithelial origin only
What is the origin of the term oncology?
- Galen was the first to use onkos to describe tumors
Where do carcinomas originate from?
Epithelium
What are the 2 general types of tumors/ what are they based on?
Benign/ Malignant
- based on histological features/ expected clinical outcome
What is the difference between a benign/ malignant tumor?
Benign- confined to tissue of origin/ rarely cause harm
Malignant- invade locally and distantly/ form colonies in other organs
What are metastases?
- colonies malignant tumors form in other organs
What is metastasis?
- the process of distant invasion of malignant tumors
How are tumors classified based on cell of origin?
Epithelial > Squamous/ Adeno/ Atypical
Non-Epithelial > Sarcomas/ Hematopoietic/ Neuroectodermal
What are the types of carcinoma based on cell of origin?
Squamous cell carcinoma > arises from epithelium with protective function/ formed by flattened (squamous) cells
Adenocarcinoma > arises from epithelium with glandular/secretory function
Atypical carcinomas > do not fit above categories
What is an example of an atypical carcinoma?
Small cell lung carcinoma
What are some common sites of epithelial tumors?
Skin/ Mammary gland/ Prostate/ GI tract/ Lung
Can you have 2 types of carcinoma that arise from epithelium of same organ?
yes- ex) squamous cell carcinomas/ adenocarcinomas of both esophagus/ lung
What are some steps in the progression from normal > malignant epithelium?
Hyperplasia/ Metaplasia/ Dysplasia
What is hyperplasia?
- ↑ growth of cells/ tissue, but normal cell features/ histology
- typical of benign tumors
What is metaplasia?
- type of epithelial cell layer is replaced by cells of another epithelial type that are normally not in that site within an organ
What is an example of metaplasia?
Barrett’s Esophagus (pre-cancerous condition)
- substitution of squamous > glandular epithelium in esophagus
- invader epithelium appears normal under microscope, but the condition is known to be pre-cancerous
What are 5 characteristics of dysplasia?
- loss in uniformity of individual cells
- loss of cell polarity
- ↑ variability in nuclear shape/size = Pleomorphism
- ↑ nuclear : cytoplasm ratio
- mitotic figures more abundant/ mislocalized
What is pleomorphism?
↑ variability in nuclear shape/ size
What is neoplasia?
= new growth
What is a neoplasm?
- abnormal mass of tissue > growth exceeds/ uncoordinated with that of normal tissue
What are neoplastic cells said to be/ why?
= Transformed
- continue to replicate/ oblivious to regulatory influences in tissue environment
What do the synonyms neoplasm/ tumor refer to?
- both pre-invasive (benign) and invasive (malignant) tumors
Why are all pre-invasive tumors considered benign, regardless of their size?
- confined to epithelial compartment by a still present basement membrane
What must happen for an epithelial tumor to be considered malignant?
- must breach the basement membrane > invade surrounding stroma
What is anaplasia?
“to form backwards” > undifferentiated
- a landmark of malignancy
What are undifferentiated neoplasms said to be?
Anaplastic
Are all malignant tumors anaplastic?
No- all anaplastic tumors are malignant, but not all malignant tumors are anaplastic
What are some characteristics of anaplasia?
- cell/ nuclear pleomorphism (variation in shape/size)
- hyperchromatic/ clumped chromatin
- ↑ nuclear : cytoplasm ratio (1:1 or higher)
- large nuclei/ nucleoli
- atypical/ numerous mitoses
- apical-basal polarity completely lost
What should you do if trying to determine if a tumor is malignant?
- check for loss of basement membrane
- do not look for anaplasia (not all malignant tumors = anaplastic)
What are anaplastic tumors sometimes called?
CUP = cancer of unknown primary
- can not be tracked to cell of origin since so undifferentiated
What are the types of non-epithelial tumors?
Sarcomas- arise from mesenchymal/ stromal cells (connective tissues)
Hematopoietic tumors > leukemia/ lymphoma
Neuroectodermal tumors > arise from cells of CNS/ PNS, derived from neural crest (neuroectoderm)
What is an exception of a tumor with cells derived from the neural crest but not neuroectodermal?
Melanoma
- melanocytes originate in neural crest but are not part of CNS/PNS
What cells do sarcomas arise from?
- stromal/ mesenchymal cells (connective tissues)
> Fibroblasts/ Adipocytes/ Osteoblasts/ Myocytes
What are the 2 types of hematopoietic tumors/ what are they derived from?
Leukemia- from hematopoietic lineages that originate in bone marrow
Lymphoma- from lymphoid tissue (lymphocytes/ derivatives)
Where do leukemias/ lymphomas arise?
Leukemia- originate in bone marrow/ move freely in circulation
Lymphoma- typically solid tumor in lymph nodes/ lymphoid tissue
What is the convention for naming benign epithelial/ stromal tumors?
- ends with the suffix “oma”
- preceded by prefix that denotes cell of origin
What is the convention for naming malignant epithelial/ stromal tumors?
- ends with the suffix “carcinoma” or “sarcoma”
- preceded by prefix that denotes cell of origin
What are adipocyte tumors called?
Benign = Lipoma/ Malignant = Liposarcoma
What is the term for a benign tumor of squamous cell origin?
Papilloma
What is the term for a benign tumor of epithelial origin with glandular/ secretory function?
Adenoma
What is a papilloma?
- benign tumor of squamous cell origin
How are leukemias classified?
- Degree of cell differentiation > Acute/ Chronic
- Hematopoietic precursor origin > Myelogenous/ Lymphocytic
What is the difference between acute/ chronic leukemias?
Acute- characterized by immature blast cells
Chronic- characterized by well-differentiated leukocytes
What type of leukemia has a more rapid/ fatal course in untreated patients?
Acute leukemia (immature blast cells)
What scientist is responsible for leukemia classification?
Rudolf Virchow
What is the cancer of plasma cells called?
Multiple myeloma
What is Hodgkin’s lymphoma characterized by?
- presence of classic Reed-Sternberg cells
What is the neuroectodermal malignancy of glial cells? (CNS not neurons)
Glioblastoma multiforme
What are NETs?
Neuroendocrine tumors
- epithelial tumors with predominant neuroendocrine differentiation
- have own class, not a type of carcinoma
Although the term NET/ neuroendocrine suggests that tumor cell origin is the neural crest/ they have endocrine function, what is true of most of these neoplasms?
- cells of endodermal origin
- express markers of both neural/ epithelial cells
- arise in different organs of body
What is the clonal evolution theory of the origin of cancer?
Monoclonal tumors/ Polyclonal tumors
- normal cells > transformation to cancerous behaviour
Who proposed cancer as a monoclonal genetic disease?
What did he find?
Peter Nowell
1. Gentic changes are important for cancer development
2. Tumors can arise from mutations in a single-cell
> Philadelphia chromosome (chromosome 9 > 22 translocation) in CML
Why do we get cancer?
Time- cancer ↑ with age
Environment- environmental factors
Inheritance
What scientist discovered the mutability of DNA suggested cancer origin?
Hermann Muller
- cancer arises due to mutations in genome
- genes mutate when exposed to radiation
What scientist found that chemical carcinogens act as mutagens?
What did he find?
Bruce Ames
- potent mutagens are potent carcinogens
- not always case > some carcinogens not mutagens = tumor promoters
