Chapter 5: Neoplasia Flashcards
What are the two structural components of a tumor?
Parenchyma and stroma
This component of a tumor is composed of transformed cells that are neoplastic and clonal. This components also determines the biological nature (aggressiveness) of the cancer.
Parenchyma
This component of a tumor is composed of supportive tissue and is non-neoplastic. This component is involved in long-term tumor survival.
Stroma
These are benign epithelial neoplasms producing or derived from glandular tissue.
Adenoma
These are benign epithelial neoplasms which have finger-like fronds.
Papilloma
These are benign tumors of capillary endothelial cells.
Hemangioma
These are benign tumors of adipose tissue.
Lipoma
These are benign tumors of smooth muscle (“fibroid”).
Leiomyoma
These types of malignant tumors are formed from mesenchyme (mesoderm) and can develop at any age. Examples include bone, muscle, vasculature.
Sarcomas
These types of malignant tumors are formed from epithelia (ectoderm, endoderm) and most commonly occur in mid to late adulthood. Examples include lung, breast, and colon.
Carcinoma (>90% of cancers)
These types of malignant tumors are formed from multiple germ cell layers.
Teratomas
This is the most common benign tumor of the female breast. It contains two tissue types and is only fibrous neoplasia.
Fibroadenoma
This is a benign tumor of tissue native to a particular site. It is well-differentiated.
Hamartoma
This is a mass that projects from a mucosal surface.
Polyp
This is the first phase of carcinoma progression and is characterized by disorderly proliferation, cells are irregular, and non-neoplastic.
Dysplasia
This is the second phase of carcinoma progression and is characterized by dysplasia throughout the epithelia. It is well-localized and has no penetration of the basement membrane.
Carcinoma in situ: early neoplasm
This is the third phase of carcinoma and involves local destruction of cells, penetration of the basement membrane, and the most likely to metastasize.
Invasive carcinoma: more aggressive
What are the four characteristics of neoplasia?
- Differentiation and anaplasia
- Rate of growth
- Local invasiveness
- Metastasis
This characteristic of neoplasia is used to describe how closely cells resemble their precursors both structurally and functionally.
Differentiation
This characteristic of neoplasia is used to describe a loss of differentiation.
Anaplasia
What is the rate of growth of a benign tumor? Malignant?
Benign: slow and controlled
Malignant: fast and uncontrolled
In terms of local invasion, how would benign and malignant tumors be described?
Benign: well-localized, isolated, non-invasive, and likely to be encapsulated
Malignancy: is destructive, has progressive invasion (local and distant), and is less likely to be encapsulated
This characteristic of neoplasia is used to describe secondary implantation into remote tissue and is the most reliable indicator of malignancy.
Metastasis (mets)
This method of metastasis is characterized by the invasion of natural body caivites by cancer cells.
Seeding within body cavities (ovaries, CNS, ventricular system)
This method of metastasis is the most common mode of cacinoma metastasis and is determined by site and tumor parenchyma.
Lymphatic spread
In lymphatic spread of cancer, what is typically the first area to be affected by?
Sentinel lymph node
This method of metastasis is very rapid and is the most common mode of sarcoma metastasis.
Hematogeneous spread
In hematogeneous spread of cancer, what is typically the first area to be affected?
Capillary beds
This is the study of health/disease in populations.
Epidemiology
Overall cancer rates increase with age. When do they typically occur?
At the age extremes
What are the three categories of hereditary cancer?
- Autosomal dominant cancer syndromes
- Autosomal recessive syndrome
- Familial cancer of uncertain inheritance
This type of hereditary cancer is due to a single gene mutation that is inherited. It is usually named by its marker phenotype (BRCA1).
Autosomal dominant cancer syndromes
This type of hereditary cancer is due to two altered alleles leading to genomic instability. Defective DNA repair enzymes are present and the best example of this is Xeroderma pigmentosa (sensitivity to UV light).
Autosomal recessive syndrome
This type of hereditary cancer is the most sporadic cancer and has some familial association. There is no marker phenotype and has multifactorial inheritance.
Familial cancer of uncertain inheritance
This is the formation of cancer.
Carcinogenesis
What are the primary targets of genetic damage related to carcinogenesis?
Regulatory genes
What are the four types of regulatory genes that could be involved in carcinogenesis?
- Proto-oncogenes
- Tumor suppressor genes (TSGs)
- Apoptosis genes
- DNA repair genes
This regulatory gene is a normal gene that regulates cellular growth. When genetically altered, they become oncogenes.
Proto-oncogene
This gene is associated with a gain of function and the alteration of 1 allele (dominant).
Oncogenes
This gene is associated with a loss of function and the loss of 2 alleles (recessive).
Tumor suppressor genes
This term is used to describe the number and appearance of chromosomes in the nucleus.
Karyotype
This term is used to describe an abnormal number of chromosomes.
Aneuploidy
What are the three types of structural abnormalities?
- Balanced translocations
- Deletions
- Gene amplification
These are non-coding RNA molecules that function to inhibit gene expression. They also suppress translation.
MicroRNAs
These are heritable changes of gene expression. They are not mutations.
Epigenetics
Genes are “silenced” by what?
- DNA methylation
- Histone modification
What are the hallmarks of cancer?
- Evading apoptosis
- Self-sufficiency in growth signals
- Insensitivity to anti-growth signals
- Tissue invasion and metastasis
- Limitless replicative potential
- Sustained angiogenesis
What are some emerging features of cancer that could be added to the original hallmarks?
- Change in energy metabolism (aerobic glycolysis)
- Evasion of the immune system
- Genomic instability
- Tumor-promoting inflammation
How do cancer cells express self-sufficiency in growth signals?
- Produce own GFs
- Stimulate stromal GFs
- Altered GF receptors
This is a good example of an overexpressed growth receptor. It is overexpressed in many cancers, but the most common is breast cancer.
HER2 (Human epidermal GF receptor 2)
What are some common signal transduction mutations?
- RAS: mutated in 30% of all tumors
- ABL: mutated in many leukemias
What is a common nuclear transciption factor? CDK activation and aerobic glycolysis are charateristic.
MYC gene
What controls the restiction point G1-S phase transition in the cell cycle?
Cyclin proteins (CDKs and CDKIs)
These genes encode inhibitory proteins, normally decrease cellular proliferation, and regulates growth (“apply brakes”).
Tumor suppressor genes (TSGs)
What is the “two-hit hypothesis”?
Both alleles must be inactivated (hit)
-There is a change in phenotype
This tumor suppressor gene is the “governor of the cell cycle”. It governs the G1-to-S checkpoint. It is dysfunctional in many cancers and viruses may inactivate it.
RB gene
This tumor suppressor gene is the “guardian of the genome”. It is commonly altered in all cancers and it maintains DNA integrity.
TP53 gene
This term is used to describe reversible cell cycle arrest (G1). There is minor DNA damage and an increase in repair genes.
Quiescence
This term is used to describe a permanent cell cycle arrest. There is major DNA damage and has failed repair.
Senescence
This is programmed cell death.
Apoptosis
This condition is characterized by a mutation in the TP53 gene and results in multiple tumors.
Li-Fraumeni syndrome
This apoptotic pathway is characterized by death receptors, TNF, and caspase-8.
Extrinsic apoptosis pathway
This apoptotic pathway is charcterized by DNA damage and caspase-9.
Intrinsic apoptosis pathway
Both extrinsic and intrinsic apoptotic pathways stimulate what caspase?
Caspase-3 (executioner)
When angiogenesis occurs in tumor cells, what do the blood vessels typically look like?
Poorly organized: leaky, dilated, and tortuous
What are the steps of the invasion-metastasis cascade?
- Invasion of ECM
- Vascular spread: dissemination and homing
- Micrometastases grow and invade
What are the steps involved with invasion of the ECM by cancer cells?
- Loosening of tumor cells
- Breakdown of ECM
- Changes in ECM attachment
- Migration of tumor cells
What is the “glue” that holds cells together?
E-cadherin
What is the most common site of vascular metastasis for cancer?
1st capillary bed
What are three DNA repair systems?
- Mismatch repair
- Nucleotide excision repair
- Homolgous recombination repair
What condition is characterized by a defective nucleotide excision repair system?
Xeroderma pigmentosum
What are some general categories of carcinogenic agents?
- Chemical
- Radiant energy (irradiation)
- Microbial (Helicobacter pylori)
What are the two types of chemical carcinogens and what are some examples of each?
- Direct-acting: no metabolic conversion (chemotherapy meds)
- Indirect-acting: require metabolic conversion (tobacco smoke, fossil fuel exhaust, smoked or broiled meats)
What are the mechanisms of chemical carcinogens?
- Cause genetic alterations
- Specific target genes
- Augmented by non-carcinogenic promoters
What is radiation carcinogenesis characterized by?
Formation of pyrimidine dimers
What is the most common form of cancer in the US?
Skin cancer
This is an oncogenic RNA virus that is transmitted by sex, blood, and breast feeding. The TAX gene, which increases cyclins and decreases TP53, is involved.
Human T cell lymphotropic virus-1 (HTLV-1)
What are some examples of oncogenic DNA viruses?
- Human papillomaivrus (HPV)
- Epstein-Barr virus (EBV)
- Hepatitis B and C viruses (HBV, HCV)
- Kaposi sarcoma herpesvirus (KSHV) a.k.a. human herpesvirus-8 (HHV-8)
This oncogenic virus causes genital warts, squamous cell carcinomas, and influence many hallmarks of cancer (activation of cyclins to increase growth, decrease apoptosis, resist cellular senescence, and degrades p53).
Human papillomavirus (HPV)
This oncogenic DNA virus causes infectious mononucleosis and its genes stimulate B cell proliferation, which inhibits apoptosis by decreasing macrophage and T cell activity.
Epstein-Barr virus
This oncogenic DNA virus has a strong association with liver cancer. Infection leads to the inhibition of apoptosis.
Hepatitis B and C viruses
This was the first “cancer bacteria” to be discovered (Gastric adenocarcinomas, gastric lymphomas).
Helicobacter pylori
What are some antitumor effector mechanisms?
- Cytotoxic T cells (CD8+ T cells)
- Natural killer cells
- Macrophages
Cancer is the most common among the immunocompromised. True or False?
True
This is unexplained weight loss, weakness, and anorexia due to cancer. It is irreversible with nutrition and indicates end-stage cancer.
Cancer cachexia (wasting syndrome)
These are features associated with cancer development. They are not associated with invasion and some examples include hypercalcemia, cushing syndrome, polycthemia, and hypertrophic osteoarthropathy.
Paraneoplastic syndromes
Grading (I-IV) and staging of cancers are based on what?
The degree of cellular differentiation
How many stages of cancer are there and how are they determined?
- Stage 0-IV
- Determined by the size of the primary tumor, lymph node involvement, and presence of metastasis.
What are three laboratory methods of cancer diagnosis?
- Biopsy
- Fine-needle aspiration
- Cytologic smear (Pap smear)
What are tumor markers?
Enzymes or hormones associated with tumor growth
What substance indicates problems with the prostate gland when found in high amounts?
Prostate-specific antigen
