Tumour Pathology Flashcards Preview

Principles of Disease 16 > Tumour Pathology > Flashcards

Flashcards in Tumour Pathology Deck (36)
1

Describe the main differences between benign and malignant tumours

Both differ in various ways:
• Growth pattern
• Presence of capsule
• Invasion
• Presence of metastases
• Differentiation
• Appearance of tumour cells
• Function
• Behaviour

2

Describe the properties of benign cancer cells

• Non-invasive growth pattern
• Usually encapsulated
• No evidence of invasion
• No metastases
• Cells similar to normal in function and appearance
• Benign tumours are “well-differentiated”
• Rarely cause death

3

Describe the systemic effects of cancer

• Secretion of hormones
• Weight loss-cachexia – unwanted, though can also be due to obstruction etc.
• Paraneoplastic syndromes
• Effects of treatment

4

Describe the local effects of cancer

Pressure
Obstruction
Tissue destruction during invasion
Bleeding due to damage of vessels during invasion
Pain due to pressure on nerves
Effects of treatments e.g. IV infusion reactions

5

Identify the concepts of neoplasia and intraepithelial dysplasia

Dysplastic = abnormal growth or development of existing tissue.
Neoplastic = relates to a new growth or tumor.

6

Describe the cell cycle of normal cells

Mitosis:
• Mechanism of cellular replication
• Nuclear division plus cytokinesis
• Generates two identical diploid daughter cells
Cell Cycle = time interval between mitotic divisions. Called interphase where the chromosomes and cellular contents are duplicated.

7

Outline the process of carcinogenesis and describe its effects on the cell cycle. 


• Cancer is a genetic disease
• Carcinogenesis is caused by mutation of genetic material that upsets the normal balance between proliferation and apoptosis (cell death)
• Uncontrolled proliferation of cells leads to tumours
• Only mutations in genes regulating cell division, apoptosis, and DNA repair cause a cell to lose control of proliferation via cell cycle dysregulation

8

List the major aetiological agents of cancer. 


• Non-lethal genetic damage - Environmental agents e.g. Chemicals, Radiation, Oncogenic viruses

• Inherited

• Geographic and environmental factors

• Age

9

Describe the properties of a cancer cell

• Altered genetics
– Loss of tumour suppressor genes
– Gain of function of oncogenes
• Altered cellular function
– Tumour-related proteins
• Abnormal morphology
• Cells capable of independent growth
• But no single feature is unique to cancer cells

10

What is the clinical significance of cancer biomarkers?

• Screening
• Diagnosis
• Prognostic- Identifying patients specific outcome
• Predictive - who will respond to a particular therapy

11

Give some examples of cancer biomarkers

Alpha-fetoprotein
• Teratoma of testis
• Hepatocellular carcinoma
Carcino-embryonic antigen (CEA)
• Colorectal cancer
Oestrogen receptor
• Breast cancer
Prostate specific antigen
• Prostate cancer

12

Describe some clinically useful predictive biomarkers

Kras (GTPase)
– Colorectal cancer
EGFR (epidermal growth factor receptor)
– Lung cancer
Her2 (neu in rodents, EGFR associated with aggressive breast cancers)
– Breast cancer
– Gastric cancer
Braf (protooncogene that helps direct cell growth)
– Melanoma

13

How can we identify cancer cells by appearance alone?

• Cellular and nuclear pleomorphism
– Marked variation in size and shape
• Mitoses (dividing cells) present and often abnormal

14

What usually worsens the prognosis of cancer?

High degree of angiogenesis, invasion and cancer spread

15

Describe the different modes of cancer spread

• Local spread
• Lymphatic spread
• Blood spread
• Trans-coelomic spread

16

Describe some common sites of metastases

• Liver
• Lung
• Brain
• Bone - Axial skeleton e.g. vertebrae, pelvis
• Adrenal gland

17

Where do breast cancers commonly metastasise?

Bone

18

Where do prostate cancers commonly metastasise?

Bone

19

Where do colorectal cancers commonly metastasise?

Liver

20

Describe two hormones that are abnormally produced in certain cancers

ACTH - lung cancer
ADH - lung cancer

21

Define paraneoplastic syndromes

Syndromes or symptoms that cannot be explained by local or metastatic effects of tumours, caused by humoral factors e.g. neuropathy, myopathy. Thought they may be caused due to immune or hormonal factors

22

Describe the importance of cyclins, cycling dependent kinases and cyclin dependent kinase inhibitors in cancer

Many genes mutated in cancer regulate the cell cycle
Two regulatory pathways frequently disrupted -
1. The cyclin D-pRb-E2F pathway
2. p53 pathway

Active CDK/cyclin complexes phosphorylate target proteins which results in activation/inactivation of that substrate, which regulate events in the next cycle phase.

pRb is hypophosphorylated, and is phosphorylated by CDK/cyclin complexes as cells progress through the cell cycle. Hypophosphorylated/active Rb inactivates E2F, while phosphorylated/inactive pRb loses affinity for E2F. Free E2F transcription factor activates vital target genes and is a potent stimulator of cell cycle entry. If this system is not regulated, uncontrolled progression through the cell cycle occurs.

23

Where in the cell cycle are cancer cells usually dysregulated and why?

Virtually all cancers are dysregulated at G1-S because of mutation in one of four genes:
o Rb, CDK4, cyclin D and p16

24

What is p53, its function and its role in cancer development?

•p53 is a gene that codes for a protein that regulates the cell cycle and hence functions as a tumor suppressor gene. Maintains genomic integrity
• p53 levels increase in damaged cells and induces cell cycle arrest at G1 to allow DNA repair
• Severe damage: p53-induced apoptosis (programmed cell death)
• Cells with mutated p53 do not G1 arrest or repair damaged DNA and these genetically damaged cells proliferate and form malignant neoplasms

25

Define tumour suppressor genes

Normal growth-inhibiting genes that discourage cell growth or temporarily halt cell division to carry out DNA repair. Huge role in carcinogenesis
• Genes negatively regulating mitosis - Rb
• Genes regulating apoptosis
• Genes regulating DNA repair

26

Define proto-oncogenes

Normal genes that promote normal cell growth and mitosis

27

Describe the two hit hypothesis

The Knudson hypothesis, also known as the two-hit hypothesis or multiple-hit hypothesis, is the hypothesis that cancer is the result of accumulated mutations to a cell's DNA

28

What % of cancers are inherited?

5-10%

29

Whats the difference between inherited cancer and familial cancer?

Inherited cancer syndromes
• Strong family history of uncommon site-specific cancers
• Autosomal dominant inheritance of a single mutant gene
– Increased risk of second cancers eg bone sarcomas

Familial cancers
• Family clustering of cancers but individual predisposition unclear
• Multifactorial inheritance
• Early age of onset
• Multiple/bilateral tumours

30

Name some inherited cancer syndromes

Familial retinoblastoma
Familial adenomatous polyposis
Multiple endocrine neoplasia
Neurofibromatosis
Von Hippel-Lindau syndrome

31

Name some familial cancers

• Some Breast cancers
• Some Ovarian cancers
• Non-FAP colon cancers

32

How do oncogenes arise from protooncogenes?

Oncogenes are derived from proto-oncogenes, which are activated by:
o Alteration of proto-oncogene structure
• Point mutation
• Chromosome rearrangements + translocations
o Dysregulation of proto-oncogene expression
• Gene amplification
• Overexpression

33

Name some cancers caused by the over expression of some proto-oncogenes

Burkitt lymphome - over expressed c-myc in IgH gene

Mantle cell lymphoma - over expressed cyclin D1 in IgH gene

34

Name some cancers caused by recombination of proto-oncogenes to form chimaeric proteins

Chronic myeloid leukaemia

35

Describe how aetiological factors of cancer disrupt the cell cycle

Viruses - insert genomes near protozoans-oncogenes and viral promoter causes over expression or they can insert oncogenes into genome

Chemical - Adduct formation at particular chromosome sites lead to activation of oncogenes and suppression of anti-oncogenes e.g. benzopyrene

36

Name some DNA viruses that cause cancer

DNA viruses known to cause cancer in humans
– HPV (cervical cancer)
– Hepatitis B (liver cancer)
– EBV (Burkitt lymphoma)