neoplasia Flashcards
5 characteristics of anaplasia
- pleomorphism (variation in cell shape and size
- nuclear hyperchromatism (intensely basophilic nuclei)
- increased nuclear/cytoplasmic ratio compared to normal cells
- atypical nuclei (variation in shape and size)
- numerous and atypical mitoses
most severe form of epithelial dysplasia which has all of the microscopic features of cancer, but the atypical cells have not invaded into the host
carcinoma-in-situ
____ tumors tend to have a capsule, which is a compressed band of _____ at the periphery of the tumor
benign; fibrous connective tissue
hemangioma and neurofibroma are common exceptions
the ____ quality is the most reliable means for distinguishing the malignant nature of a tumor
infiltrative
____ is considered the best indicator of malignancy
presence of metastasis
3 ways that malignancies spread
- seeding within body cavities (like the peritoneal cavity)
- lymphatic spread (commonly seen in carcinomas, resulting in lymph node metastases)
- hematogenous spread- favored by sarcomas; lung and liver frequent sites of metastasis in this case
3 well-defined genetic influences on cancer
- inherited cancer syndromes, AD (Rb, MEN)
- defective DNA repair syndromes, AR (xeroderma pigmentosum, ataxia telangiectasia)
- familial cancers (colon, breast, ovarian)
acquired preneoplastic disorders (persistent regenerative cell replication)
- squamous metaplasia and dysplasia of bronchial mucosa
- endometrial hyperplasia and dysplastic proliferations
- leukoplakia of the oral mucosa, vulva, penis
- villous adenomas of the colon
3 classes of normal regulatory genes - principal targets of genetic damage
- protooncogenes
- cancer suppressor genes
- apoptosis regulatory genes
____ are also important in carcinogenesis; if these genes are disabled, the _____ increases and the _____ increases
DNA repair genes; frequency of mutations; rate of neoplastic transformation
6 hallmarks of cancer
- self-sufficiency in growth signals
- insensitivity to growth inhibitory signals
- evasion of cell death
- limitless replicative potential
- development of sustained angiogenesis
- ability to invade and metastasize
factors susceptible to cancer in development of self-sufficiency in growth signals
- growth factors
- growth factor receptors
- signal-transduction proteins
- nuclear transcription factors
- cyclins and cyclin-dependent kinases (CDKs)
growth factor receptor commonly overexpressed
epidermal growth factor receptor family
ERBB-1 in squamous cell carcinoma of the lung
ERBB-2 (HER/NEU) amplified in some breast cancers
most commonly mutated proto-oncogene
RAS gene (normal cytoplasmic signal-transducing protein)
most common overexpressed nuclear transcription factor
MYC gene (activates transcription of cyclin D1, a gene whose product drives cells into the cell cycle)
first tumor suppressor gene to be discovered
retinoblastoma (Rb) gene
single most common target for genetic alteration in human tumors
TP53 tumor suppressor gene
___ loss of ____ is found in virtually every type of cancer; usually due to _____
homozygous loss of TP53; somatic mutation
condition in which families have one aberrant TP53 gene, resulting in a markedly increased rate of cancer for affected individuals
Li-Fraumeni syndrome
____ is the prototypic anti-apoptosis gene activated by ____; found in ____
BCL2; translocation; low-grade lymphomas
2 major phases of metastasis
- invasion of the ECM
2. vascular dissemination and adhesion/homing of tumor cells
steps of invasion of ECM
- detachment of tumor cells from one another
- attachment of tumor cells to matrix components
- degradation of ECM
- migration of tumor cells
once in the circulation, tumor cells adhere to _____, followed by _____
vascular endothelium; basement membrane transmigration
the dist of tumor metastases can generally be predicted by the _____ and _____
location of the primary tumor and its vascular or lymphatic drainage
2 methods of organ tropism
- organ specific endothelial adhesion molecules bind tumor cell ligands
- chemokine receptors on tumor cells home to sites where specific ligands are readily produced
conditions with inherited defects in DNA repair
- hereditary nonpolyposis colon cancer syndrome
- xeroderma pigmentosum
- bloom syndrome, ataxia telangiectasia, fanconi anemia
HNPCC syndromes are familial cancers of the colon resulting from defective genes involved in ______ and evidence of ______
DNA mismatch repair; microsatellite instability (MSI)
xeroderma pigmentosum involves a defective _______; sunlight (UV light) causes _____ in DNA, halting replication with inability to repair these altered residues
nucleotide excision repair system; pyrimidine cross-linking
Bloom syndrome, ataxia telangiectasia, and fanconi anemia are ____ disorders characterized by _____; called _____
AR; hypersensitivity to Dna damage; fragile dna disorders
familial breast cancer genes (BRCA1 and BRCA2) involved with _____, may also have _____ roles
dsDNA breaks; tumor suppressor
karyotypic changes in tumors
- balanced translocations
- deletions
- gene amplifications
balanced translocations extremely common especially in _____ (example is _____ in ____)
hematopoietic neoplasms; philadelphia chromosome; chronic myelogenous leukemia
most carcinogens are ____ and require some _____
indirect; metabolic conversion
indirect carcinogens are called _____ and active end-products are termed _____
procarcinogens (i.e. polycyclic hydrocarbons); ultimate carcinogens
all carcinogens are highly reactive _____, interacting with the _____ and inducing genetic damage
electrophiles; electron-rich DNA molecule
3 major classes of carcinogenic agents
- chemicals
- radiation
- oncogenic viruses
some carcinogens can be augmented by ____, agents that have little inherent transforming ability
promoters (carcinogen serves as initiator of mutagenic event)
example of an RNA oncogenic virus
HTLV-I (human T cell leukemia virus type I)
HTLV-I is associated with a form of _____ in certain parts of ____ and the _____
T cell leukemia/lymphoma (develops in about 3-5% of infected people after a long 20-50 year latent period)
DNA oncogenic viruses are transforming DNA viruses that form ____ associations with the host cell _____
stable; genome
3 types of DNA oncogenic viruses
- human papillomavirus (HPV)
- epstein-barr virus (EBV)
- hepatitis B virus (HBV)
some types of HPV (1, 2, 4, 7) cause _____ or _____
benign squamous papillomas; verruca vulgaris (wart)
HPV types 16 and 18 are associated with the development of _____ and _____
uterine cancer; oropharyngeal (tonsillar) cancer
EBV implicated in pathogenesis of:
Burkitt lymphoma, B-cell lymphoma in immunosuppressed patients, Hodgkin lymphoma, and nasopharyngeal carcinoma
HBV linked to development of ______
hepatocellular carcinoma
the concept of _____ refers to the recognition and destruction of non-self tumor cells when they appear
immune surveillance
antigens only associated with tumor cells
tumor-specific antigens
2 examples of tumor-specific antigens
cancer-testis antigens
MAGE-1 (melanoma-associated antigen)
these are antigens that may be found on normal cells, but may be overexpressed or represent a specialized function of the cells
tumor-associated antigens
tumor-associated antigens that represent a specialized function of the cells
differentiation-specific antigens
example of a differentiation-specific antigen
prostate-specific antigen (PSA)
4 antitumor effector mechanisms
- cytotoxic (CD8+) T lymphocytes
- natural killer (NK) cells
- macrophages
- humoral mechanisms
CD8+ T lymphocytes play a role against ____ neoplasms, such as ____
virus-induced; Burkitt’s lymphoma
NK cells are lymphocytes that can kill tumor cells without _____; may be the ___ line of defense against tumors
prior sensitization; first
macrophages may collaborate with ____ and ____ to destroy tumor cells; may act by mechanisms used to destroy ____ or by producing ____
T cells; NK cells; microbes; TNF-alpha
humoral mechanisms include either activation of _____ or induction of _____ by NK cells
complement; antibody-dependent cytotoxicity
3 host defenses against tumors
- tumor antigens
- antitumor effector mechanisms
- immunosurveillance
how cancers develop in immune competent individuals
- selective outgrowth of antigen-negative variants
- loss or reduced expression of histocompatibility antigens
- lack of co-stimulation
- immunosuppression
tumor cells do not express normal levels of _____, thereby escaping attack by _____
HLA class I; cytotoxic T cells
effects of tumor on host
- location
- hormone production
- ulceration
- cachexia
- paraneoplastic syndromes
____ and _____ arising from the beta cells of the pancreatic islets may produce _____ which may be fatal
adenomas; carcinomas; hyperinsulinism
hormone production is more frequent in _____ tumors
well-differentiated, benign
cachexia may involve ___ and ____
TNF; IL-1
examples of paraneoplastic syndromes
hypercalcemia
cushing’s syndrome
nonbacterial thrombotic endocarditis
paraneoplastic pemphigus
attempt to assess the aggressiveness of a malignancy based on such criteria as the degree of cytologic differentiation of the tumor cells and the number of mitoses
grading (can range from I to IV)
I - most differentiated
IV- least differentiated
a method of estimating the size or extent usually done using clinical examination coupled with imaging studies (plain radiographs, CT, MRI)
staging
used primarily as a screening method for cervical Ca. Now being supplemented by HPV testing
cytologic (papanicolaou) smears
specific antibody-guided detection of tumor-specific or associated antigens to determine the precise classification or subclassification of a tumor
immunocytochemistry
Used routinely in classification of leukemias and lymphomas. Surface markers and DNA ploidy analysis
flow cytometry
looking for tumor-associated enzymes, hormones and other tumor markers in the blood. Prostate-specific antigen (PSA) is a good example
biochemical assays
use of fluorescent in-situ hybridization (FISH) or polymerase chain reaction(PCR)-based methods gives important diagnostic and prognostic information. “Personalized” medicine
molecular diagnosis
