Week 7 Nelson - Neoplasia Flashcards
Define Neoplsia.
“new growth”
A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which invoked the change.
What is a benign neoplasm?
- Cannot spread to other tissues (does not metastasize)
- not locally invasive
What is a malignant neoplasia?
Have the capability to metastasize.
Tend to be locally invasive and distroy adjacent structures.
What is a “lack of differentiation” called?
Anaplasia
Define metaplasia.
Potentially reversible change in which one differentiated cell type is replaced by another.
Define Hyperplasia.
Increase in the number of cells.
- can form tissue mass
- will regress once the stimulus is removed
Define hamartoma.
Non-neoplastic disorganized aggregate of mature tissues indigenous to the site of origin.
Define choristoma.
A heterotopic rest of mature cells.
(ex. pancreatic tissue in submucosa of stomach)
Define dysplasia.
Disordered growth and cytologic changes seen in epithelium.
-can progress to carcinoma in situ, but not always
What are the six main categories of Neoplasms?
(Hint: according to cell or tissue of origin)
- Tumors of epithelial origin (carcinoma)
- Tumors of mesenchymal origin (sarcoma)
- Tumors of hematopoietic or lymphoid origin
- Tumors of melanocytic origin
- Tumors of the CNS (brain/spinal cord)
- Tumors of germ cell origin
Define adenoma.
Benign epithelial neoplasms showing glandular differentiation.
Define papilloma.
Benign epithelial neoplasms that form papillary structures.
What is squamous cell carcinoma?
Malignant epithelial neoplasms showing squamous differentiation.
Define adenocarcinomas.
Malignant epithelial neoplasms showing glandular differentiation.
What is a teratoma?
Tumor of germ cell origin which can show differentiation in more than one germ cell layer.
What are the three pathways of metastatic spread?
- Direct seeding of body cavities or surfaces
- Lymphatic spread
- Hematogenous spread (blood)
What are the three most common cancers in men?
- Prostate
- Lung
- Colorectal
What are the three most common cancers in women?
- Breast
- Lung
- Colorectal
What type of cancer is responsible for the most cancer deaths in both men/women?
Lung cancer!
(Don’t smoke!)
What type of risk factors appear to be the dominant risk for most cancers?
Environmental
What are some environmental factors in cancer epidemiology?
- Infectious agents (HPV)
- Cigarette smoking
- Alcohol consumption
- Diet
- Obesity
- Reproductive history
- Environmental carcinogens
What role does age have in developing cancer?
1 cause of death in women 40-79 & men 60-79
Important influence on the likelihood of being afflicted with cancer.
Most carcinomas occur in older individuals (>55)
- Accumulation of somatic mutations
- Decline in immune competence
What are the four types of genes typically mutated in cancer?
- Four classes of normal regulatory genes
- growth-promoting proto-oncogenes
- growth-inhibiting tumor suppressor genes
- genes that regulate apoptosis
- DNA repair genes
Name five proto-oncogenes, their function, and the mutation that leads to an associated cancer.
- ABL
- nonreceptor tyrosine kinase activity
- translocation → chronic myelogenous leukemia
- HER
- receptor synthesis
- amplication → breast carcinoma
- MYC
- nuclear transcription
- translocation → Burkitt’s lymphoma
- N-MYC
- nuclear transcription
- amplification → Neuroblastoma
- RAS
- signal transduction
- point mutation → Lung, colon, & pancreatic carcinomas
Name three tumor suppressor genes, their functions, and associated cancers.
- APC
- prevents nuclear transcription by degrading beta-catenins (Wnt pathway)
- Familial polyposis (colorectal carcinoma)
- BRCA1/BRCA2
- regulates DNA repair
- Breast cancer (ovary & prostate carcinomas too)
- p53
- inhibits G1 to S-phase, repairs DNA, activates Bax (apoptosis)
- Lung, colon, & breast carcinoma
What are the 8 essential alterations (“hallmarks”) involved in malignant transformation of cells?
- Self-sufficiency in growth signals (proliferate without external stimuli)
- Insensitivity to growth-inhibitory signals (inactivation of tumor suppressor genes)
- Altered cellular metabolism (aerobic glycolysis/Warburg effect)
- Resistant to apoptosis
- Limitless replicative potential (immortality)
- Sustained angiogenesis
- Ability to invade and metastasize
- Ability to evade the host immune response
What are two enabling characteristics of cancer cells?
- Genomic instability
- Cancer-promoting inflammation
What is the importance of epigenetic and miRNA changes?
- Epigenetic
- Causes considerable epigenetic heterogeneity
- silencing of tumor suppressor genes
- global changes in DNA methylation
- Changes in histones
- miRNA
- control normal cell growth, differentiation, and cell survival
- altered, decreased, or overexpressed miRNA plays a role in many cancers
What is an example of chemical carcinogenesis?
Alcohol!
Associated with squamous cell carcinoma of oropharynx, upper/middle esophagus, pancreatic and hepatocellular carcinomas.
What is an example of radiation carcinogenesis?
- Ionizing electromagnetic radiation:
- X-rays, CT, gamma rays
- leukemia, lung, thyroid, breast, colon
- Ultraviolet (UV) rays
- skin cancer
What are some examples of microbial carcinogenesis?
- Human T-cell leukemia virus type 1 (HTLV-1)
- viral integration into host genome
- leads to pro-growth signalling and genomic instability
- viral integration into host genome
- Human papillomavirus (HPV)
- code for oncogenic proteins that inactivate tumor suppressors
- inhibit apoptosis
- Epstein-Barr virus
- implicated in Burkitt lymphoma
- virus acts as a polyclonal B-cell mitogen
- Hepatitis B & C
- chronic inflammation, hepatocyte death, genomic damage
How is the Warburg effect used for cancer diagnosis.
- Warburg Effect:
- tumor’s reliance on fermentation of glucose to lactate despite their being abundant oxygen. The Warburg effect is thus referred to as ‘aerobic glycolysis’.
- glucose metabolism can be used to visualize tumors in PET scan
- shows cells that preferentially take up glucose such as tumor cells & actively dividing tissues
Define cachexia.
Progressive loss of both body fat and lean muscle mass along with weakness and anorexia that is associated with cancer.
What are paraneoplastic syndromes?
- Symptom complexes in cancer-bearing individuals that cannot be explained
- either by the local or distant spread of tumor or by the elaboration of hormones indigenous to the tissue from which the tumor arose
- ex. Cushings syndrome, lung cancer, secrete ACTH
- ex. Hypercalcemia in squamous cell carcinoma of the lung due to parathyroid hormone-related protein
- ex. Venous thrombosis in pancreatic carcinoma due to secretion of mucins that activate clotting
What is grading and staging of malignant neoplasms?
- Grading
- degree of differentiation
- poor-well, 1-3
- Staging
- size and/or local degree of invasion (T)
- extent of spread to lymph nodes (N)
- presence or absence of distant metastases (M)
Describe the AJCC staging classification scheme.
- Primary Tumor (T)
- what layers tumor invades
- 0-4
- Regional Lymph Nodes (N)
- # of metastises in region lymph nodes
- Distant Metastasis (M)
- absence, presence, #of metastases in one organ, #of metastases in 1+ organ,
What is the first step in the pathologic diagnosis of neoplasms?
Obtaining a sample containing the tumor.
How does an immunohistochemical stain work?
- Primary antibody binds to tissue antigen
- Secondary antibody binds to primary antibody
- Enzyme complex binds to secondary antibody
Test with different antibodies/proteins to identify cell products or surface markers to determine where tissue is from.
How does flow cytometry work?
- cells labeled with fluorescent antibodies
- antibodies bind to specific antigens on the cells
- signal is detected allowing quantification of types of cells expressing the antigens of interest
This technique is very useful in the identification and classification of leukemias and lymphomas.
What are the applications of molecular diagnostics with regard to cancer?
- Diagnosis of malignant neoplasms
- Prognosis and treatment of malignant neoplasms
- Detection of minimal residual disease
- Diagnosis of hereditary predisposition to cancer
What is the common, major limitation of cancer biomarkers?
The biomarker is often secreted in both malignant and non-malignant conditions affecting the involved tissue.
-cannot be used for definitive diagnosis of cancer, but instead used for screening
Define prevalence.
Percentage of individuals who have the disease in the population that is tested.
Define sensitivity.
Percentage of individuals with the disease who have a positive test result.
Define specificity.
Percentage of individuals without the disease who have a negative test result.
Predictive value?
- Increasing sensitivity will decrease specificity
- Increasing specificity will decrease sensitivity
- if risk for failure to diagnose is high, test with high sensitivity
- high sensitivity test first (no false negatives)
- confirmatory high specificity test (no false positives)
