Neoplasm Flashcards
what are 3 important characteristics of neoplasm
unregulated, irreversible, and monoclonal
define the monoclonal nature of neoplasm
neoplastic cells are derived from a single mother cell
what can be used to determine clonality of a neoplasm
G6PD isoforms or androgen receptor isoforms
what is desmoplasia
the presence of abundant collagen fiber in connective tissue, giving it a firmness
what are the 2 basic components of tumors
- tumor parenchyma (neoplastic cells(
* reactive stroma (CT, fibrous tissue, blood vessels, and inflammatory cells; may be desmoplastic)
what is a fibroma
a benign tumor originating from fibrous tissue
what is a lipoma
a benign tumor originating from adipose tissue (lipid)
what is a chondroma
a benign tumor originating from cartilage
what is a osteoma
a benign tumor originating from bone
what is a hemangioma
a benign tumor originating from blood vessels
what is a lymphangioma
a benign tumor originating from lymph vessels
what is leiomyoma
a benign tumor originating from smooth muscle
what is a rhabdomyoma
a benign tumor originating from striated muscle
what is a fibrosarcoma
a malignant tumor originating from fibrous tissue
what is a liposarcoma
a malignant tumor originating from adipose tissue
what is a chondrosarcoma
a malignant tumor originating from cartilage
what is an osteosarcoma
a malignant tumor originating from bone
what is an angiosarcoma
a malignant tumor originating from blood vessels
what is a lymphangiosarcoma
a malignant tumor originating from lymph vessels
what is a leiomyosarcoma
a malignant tumor originating from smooth muscle
what is a rhabdomyosarcoma
a malignant tumor originating from striated muscle
what is the nomenclature for a benign neoplasm derived from glands
adenoma
what is the nomenclature for a benign neoplasm that produces fingerlike or warty projections
papilloma
what is the nomenclature for a benign neoplasm that forms large cystic masses
cystadenoma
what is the nomenclature for a benign neoplasm that forms a visible projection above mucosal surface
polyp
what is the nomenclature for a malignant tumor derived from glands
adenocarcinoma
what is the nomenclature for a malignant tumor derived from squamous epithelium
squamous cell carcinoma
what is the nomenclature for a malignant tumor derived from kidney cells
renal cell carcinoma
what is the nomenclature for a malignant tumor derived from liver cells
hepatocellular carcinoma (hepatoma is an old term, and it somewhat of a misnomer)
what is a biphasic neoplasm
one that is derived from both fibroblasts and glandular epithelium
what is a fibroadenoma
a benign neoplasm of breast
having well circumscribed borders is a common characteristic of what kind of tumor
benign
what is a teratoma
a germ cell tumor arising from totipotent cells in testis or ovary
ovarian teratomas are almost always benign this can be contrasted with…
testicular teratomas in adults are never benign
melanoma is an exception to general nomenclature because
they are malignant by definition
what is an anaplastic tumor
one that has no resemblance (histologically) to the tissue of origin
a tumor that is well differentiated…
closely resembles the normal cells of the tissue of origin
tumor necrosis is a feature of malignant tumors. what happens here?
rapidly growing cancers can outgrow their blood supply -> ischemia -> tumor necrosis
what are the 6 hallmarks of cancer?
- sustain proliferative signaling
- evade growth suppressors
- resist cell death
- enable replicative immortality
- induce angiogenesis
- activate invasion and metastasis
how to malignant cells sustain proliferative signaling?
- can proliferate without external stimuli
* usually consequence of oncogene activation
what is an oncogene
- originates from mutated proto-oncogene
* promotes autonomous cell growth in cancer cells
how do malignant cells evade growth suppressors
- mutated tumor suppressor genes
* 2 hit origin of cancer
why is P53 considered the guardian of the genome?
- encoded by tumor suppressor gene
* when mutated, unable to arrest cell cycle for DNA damage repair
which protein is often called the “governor of cell proliferation” and why?
- retinoblastoma protein
- encoded by tumor suppressor gene
- regulated G1/S checkpoint
what are some ways that malignant cells resist cell death
- mutations in TP53
- mutations in other genes that regulate apoptosis
- overexpression of anti-apoptotic signaling molecules (ie Bcl-2)
how do malignant cells enable replicative immortality?
- all cancer cells contain stem cells -> immortality
* also high telomerase activity
what is an important regulator of angiogenesis, which is an important hallmark of cancer
VEGF
how can malignant cells activate invasion and metastasis
- loosen cell-cell adhesion mediated by cadherins
- secrete proteases to degrade ECM
- use adhesion molecules to migrate through ECM
what type of gene accounts for the vast majority of familial cancer syndromes?
tumor suppressor genes (ie TP53, RB, P16)
mutations leading to oncogenes (less common than tumor suppressor) lead to
constitutive activation (gain of function)
what are the basic steps of polymerase chain reaction (PCR)
- denaturation of DNA
- anneal with primer
- elongation; doubled DNA with each cycle
a carcinoma is a malignancy of
epithelial cells
a sarcoma is a malignancy of
mesenchyme/soft tissues
What is the TNM staging system for cancer? and which is the most important for predicting patient outcome?
T: tumor
N: lymph nodes
M: metastasis
*metastasis most important for determining outcome
what test is recommended in all patients with colorectal cancer?
testing for lynch syndrome (and endometrial cancers in females, at least in NM)
what is lynch syndrome
a hereditary cancer cause by mutation in 1 of 4 DNA mismatch repair proteins (form of tumor suppressor gene)
what are the 4 mismatch repair proteins, and which one most commonly mutated in lynch syndrome?
MLH1 (most common)
MSH2
MSH6
PMS2
which mutations are almost never seen in lynch syndrome?
BRAF, meaning a BRAF test could be done to rule out HNPCC
what is the underlying mechanism of HNPCC or lynch syndrome
microsatellite instability
EGFR is a proto-oncogene, and mutations can cause
non-small cell lung cancer
non-small cell lung cancer is a unique lung cancer in that it is commonly seen in
never smokers, females, asians
what is the idea behind a “liquid biopsy”
tumor fragments can enter the blood stream and can be found in serum test rather than invasive biopsy
what is liquid biopsy commonly used for
- lung cancers
- resistance mutations
- patients who can’t do another biopsy
syndromic colorectal carcinoma are caused by germline mutations. examples include
- HNPCC -> mismatch repair genes including MLH1
* familial adenomatous polyposis -> APC gene
what are the signs and symptoms that usually lead to detection of cancer
- physical pressure
- organ(s) dysfunction
- systemic effects (ie fever, peri-neoplastic effects)
what is metastatic tropism?
tumors originating from a given organ preferentially seed in particular tissues
angiogenesis in tumor formation most closely resembles what type of capillary
sinusoid capillaries, which have wide spaces between endothelial cells
angiogenesis is a process seen anatomically and pathologically including
- embryonic development
- implantation of placenta
- wound healing
- many disease processes
- tumorigenesis
Receptor tyrosine kinases located on the surfaces of endothelial cells respond mainly to ___ and ___ to stimulate angiogenesis
- VEGF = vascular endothelial growth factor
* bFGF = basic fibroblast growth factor
what is the role of HIF-1α in angiogenesis?
hint: what happens to is in oxygen rich and poor states
- in oxygen rich states, proline residues on HIF-1α are hydroxylated -> ubiquitination -> proteasome degradation
- in oxygen poor states, it binds to HIF-1β, which acts as a transcription factor to stimulate VEGF production
what do tumors resemble?
- wound healing sites
* macrophages secrete many growth factors, including VEGF
what do matrix metalloproteinases (MMPs) do?
they are a family of proteases involved in the degradation of capillary basal lamina that is needed for angiogenesis
what is an important protein involved in new vessel maturation in angiogenesis?
angiopoietin 1 (Ang 1)
many tumor cell populations initially lack what ability, which is necessary for tumor expansion?
ability to track blood vessels; the “angiogenic switch” must be turned on before tumor expansion can occur
what does it mean to say that tumors have a heterogeneity of angiogenic activity?
a mix between angiogenic and non-angiogenic cells
what transition is necessary for a neoplasm to become invasive? and what does this transition involve?
- epithelial-mesenchymal transition (EMT)
* involves a transition of type of cell adhesion molecules
what factors affect where a metastasis will seed?
- blood and lymph flow from the organ of origin
* chemokines
what factors affect the efficiency of a metastasis?
differentiation, developmental and growth conditions (mitogens and growth factors)
what are the additional hallmarks of cancer that were added after the original 6?
- deregulating cellular energetics
- avoiding immune destruction
- tumor-promoting inflammation
- genome instability and mutation
infection by what organism causes 90% of stomach cancers?
H. pylori
infection by what causes nearly 100% of cervical cancers?
HPV
what infections can account for ~77% of liver cancers?
HBV and HCV
what are 3 important steps that microbes use to induce uncontrolled cellular proliferation?
- uncoupling of normal regulatory mechanisms
- prevention of host cells from undergoing apoptosis
- avoid host’s immune system
what are the 2 major phyla normally found in the gut?
bacteriodetes and firmicutes
what is the only known neoplasm that can be eliminated with abx?
MALT lymphoma; 80% associated with H. pylori
what locations can develop cancer due to infection with HPV?
cervix, vagina/vulva, anus, penis, and oropharynx
which HPV variants cause the most cervical cancers
HPV 16 and 18 cause 70% of cervical cancers and precancerous cervical lesions
E6 and E7 are 2 important genes on the HPV genome. What do they bind to in humans?
E6->p53
E7->pRB
what is the most important factor in worldwide occurrence of hepatocellular carcinoma?
HBV
how is HBV transmitted?
perinatal, sexual, blood transfusions, IV drug use
how is HCV transmitted?
blood transfusions, IV drug use
