Cancer Flashcards
Vimentin (marker)
mesencyme
Burkitt’s Lymphoma (cause)
caused by translocation t(8;14)
Active transcription of c-MYC (growth factor)
cancer of lymphoid cells
malignant lymphoma
cancer of mesenchymal origin
sarcoma
Chromogranin (marker)
neuroendocrine cells (small cell carcinoma of lung and carcinoid tumors)
Where do most mutation in p53 occur?
DNA-Binding Domain
Prevents transcription of Bax, Bak, and Bad
colloid (mucinous) carcinoma
excessive mucin is produced by tumor cells (breast, colon)
Rb Protein
Tumor Suppressor that regulates G1–> S Phase
sequesters E2F
Releases E2F when phosphorylated by Cyclin D/CDK complex
benign tumor of nerves
neurofibroma
Cohesins
hold sister chromatids together
Aberation will result in inability for sister chromatids to associate in prophase
Nitrosamine
gastric cancer
Metastasis to brain
common from cancer of lung, breast, and kidney
Parenchyma
Functional cells of an organ or neoplasm
benign tumor of meninges
meningioma
Large Scale Genomic Instability
Presence of alterations in chromosome number (aneuploidy), or chromosome structure (rearrangements, breakages, genetic insertions/deletions, etc)
This can result from changes and alterations in expression level of proteins important for regulating normal mitotic progression
Non-neoplastic, reversible forms of cell proliferation
Hyperplasia, Metaplasia, and Dysplasia (variation in size and shape of cells with loss of orientation). Normal mitosis
Margin of Benign vs Malignant
Benign: smooth, encapsulated, non-invasive
Malignant: irregular margin, no capsule, invasive
Chronic Myelogenous Leukemia (cause)
Caused by translocation t(9;22) - Philaedelphia Chromosome
Forms Bcr-Abl Fusion Protein
Abl is a kinase that activates unrestricted growth
Gleevec (imatinib) is a drug that inhibits kinase activity of Bcr-Abl
Tumor/Cancer of Placental epithelium
Benign: Hydatiform mole
Malignant: Choriocarcinoma
Bcl-2
(function, disease-association)
Sequesters Cytochrome C in mitochondria and prevents activation of caspases
Amplification due to t(14,18) transposition resluts in follicular lymphoma because B cells cannot commit apoptosis during somatic hypermutation
Staging of Tumor
Based on size, extent of spread to lymph nodes, and absence or presence of metastasis
T - tumor size
N - lymph node involvement
M - metastasis
Staging of a tumor is better correlated with prognosis than Grading
benign tumor of cartilage
chondroma
Nuclei of Benign vs Metastatic cells
Benign: normal nuclei (N/C ratio = 1:6)
Metastatic: large, hypercromatic (N/C ratio = 1:1)
oat cell (small cell) carcinoma
undifferentiated carcinoma of neuroendocrine origin, usually in lung. Cells are lymphocyte-like on microscopy
Metastasis to bone
Common from cancer of prostate, lung, breast, thyroid, and kidney
papilloma
benign tumor arising from an epithelial surface that shows finger-like projections
medullary carcinoma
soft consistency of the tumor is due to very little connective tissue stroma
Clonality of Tumors
Most tumors and neoplasms arise from monoclonal transformations
In some cases, such as familial colonic polyposis, tumors can be of polyclonal origin
Grading of Tumors
Determines aggressiveness and degree of anaplasia
5 grades; higher grade means less differentiated and worse prognosis
benign tumor of fibrous tissue and glands
fibroadenoma
Most common sites of metastatic tumor
Lung adn Liver
Biologic hallmarks of cancer
invasion and metastasis
benign tumor of smooth muscle
Leiomyoma
Lymphatic spread
Preferred route of spread in most carcinomas
Polycyclic Hydrocarbons
Benzanthracene found in cigarette smoke - associated with lung cancer
Also produced by broiling and smoking meats/fish
Arsenic
associated with skin cancer
Paraneoplastic Syndrome: Fever of Unknown Origin
Lymphoma (especially Hodgkin’s), renal carcinoma, osteogenic sarcoma
cancer of synovium
synovial sarcoma
Neoplasm
abnormal growth characterized by uncontrolled, excessive, purposeless, and almost autonomous proliferation of cells resulting in formation of a mass. Irreversible
Anaplasia
Lack of differentiation characterized by: nuclear pleomorphism (variation in size and shape), hyper-chromatic nuclei, large nucleoli, high mitotic rate, and high nuclear/cytoplasmic ratio
mucinous cystadenoma
contains mucin
4 Ways to Acitvate Oncogenes (and examples)
- Point mutation creating a “constitutively active” form of protein (RAS)
- Amplification: Increase in number of copies of gene (HER2)
- Increase in amount of protein present by moving gene to active promoter (Burkitt, Mantle Cell, Follicular)
- Translocation creating fusion protein (Bcr-Abl)
HER2
(what it does, what can go wrong, what treats it)
HER2 is a Tyrosine Kinase receptor
When activated, it stimulates a cascade that favors cell cycle progression
Some people have extra copies of this gene, so its expression is amplified, making too many receptors present on the outside of the cell
Highly associated with development of Breast Cancer
Trastuzumab is a monoclonal antibody that targets this receptor
Krukenberg tumor
ovarian metastatic tumor, usually from a gastric adenocarcinoma
clear cell carcinoma
aka renal cell carcinoma; neoplastic cells contain clear cytoplasm
Paraneoplastic Syndrome: Clubbing of fingers
lung cancer
Scirrhous (desmoplastic) carcinoma
marked fibrotic stroma that makes tumor stony hard
Hematogenous Spread
Dominant spreading route for Sarcomas
Carcinomas that spread via this route:
- Renal Cell Carcinoma
- Hepatocellular carcinoma
- Follicular Carcinoma of the Thyroid
- Choriocarcinoma
RAS
proto-oncogene that becomes an oncogene after a point mutation that leaves it constitutively activated
Active form is RAS-GTP
Mutation asociated with carcinomas, melanoma, and lymphoma
Paraneoplastic Syndrome: Myasthenia
thymoma
Paraneoplastic Syndrome: Cushing’s Syndrome
small cell carcinoma of lung; due to ACTH
Mantle Cell Lymphoma
Occurs due to amplification of Cyclin D due to transposition t(11,14)
This causes the cell to activate Rb pathway and pass the G1/S checkpoint
Benign tumors remain benign and do not undergo malignancy. The only exception is:
Adenocarcinomas of colon usually result from Ademomas
Paraneoplastic Syndromes
Symptom complexes other than cachexia in cancer patients that cannot be explained by local and distant spread of the tumor or by production of hormones indigenous to the tissue
Paraneoplastic Syndrome: Hypercalcemia
squamous cell carcinoma of lung, adenocarcinoma of breast, and renal cell carcinoma; due to PTH
Cancer of epithelial origin
carcinoma
Paraneoplastic Syndrome: Carcinoid Syndrome (seratonin, histamin, bradykinin)
Brochial carcinoid metastatic to liver
Wilm’s Tumor
Nephroblastoma; childhood malignant tumor of kidney arising from renal blastoma showing mixed embryonal tubular structures and sarcomatoid stroma
Caused by deletion of gene on Chromosome 11
Differentiation
The degree to which the tumor cells exhibit morphologic and functional resemblance to comparable normal cells
Names for neoplasm/cancer of melanocytes
Benign: Nevus
Malignant: Melanoma
Neoplastic, irreversible forms of cell proliferation
Anaplasia - greater degree of pleomorphism than dysplasia, varying degrees of differentiation. Abnormal mitosis
Paraneoplastic Syndrome: Deep Vein Thrombosis, thrombophlebitis
pancreatic cancer, GI tract cancer, lung cancer
names for tumor/cancer of mesothelium
benign mesothelioma
malignant mesothelioma
Cystadenoma
benign epithelial tumor containing fluid or semisolid material
p53
Major tumor suppressor; almost all cancers have a mutation in this pathway
Regulates Apoptosis and DNA Repair via activation of Caspases
Many points on this pathway can cause loss of this function (Amplification of Mdm2, mutated p53, Amplification of Bcl-2)
Hamartoma
localized overgrowth of mature cells normally found in an organ. DIsorganize mature cells produce a mass that looks like a tumor, but is benign. Common in lung and liver
Cancer of neuroglial cells
Malignant Glioma
Desmoplasia
Exuberant production of collagenous stroma induced by the tumor cells
Condensins
compact chromosomes
aberation will alter ability for chromosomes to properly condense in prophase
Benign tumor of striated muscle
rhabdomyoma
benign tissue of fibrous tissue and fat
fibrolipoma
Vinyl chloride
Used to make PVC pipes; causes hemangiosarcoma of liver
signet-ring cell carcinoma
adenocarcinoma where malignant cells look like signet rings microscipically. Usually in stomach
Benign tumor of fibrous tissue
fibroma
Ways cancers can spread
- lymphatics
- hematogenous
- seeding through body cavities and surfaces
Blood level is high in trophoblastic (hydatidiformmole, chorionic carcinoma) and germ cell tumors
Human Chorionic Gonadotrophin (HCG)
Asbestos
associated with lung cancer and mesothelioma
Paraneoplastic Syndrome: Hypoglycemia
Sarcomas, liver cancer; due to insulin
Neuroblastoma (cause)
Caused by gene amplification of N-Myc
Desmin (marker)
muscle
Cancer of liver
Hepatoma or Hepatocellular Carcinoma
Why do tumors grow faster than surrounding cells?
The cells themselves do not divide faster; the tumor grows quickly because a greater percentage of cells are actively dividing and fewer cells are committing apoptosis
Describe steps of metastasis
- Downregulation of E-cadhedrin leads to disassociation from surrounding cels
- Tumor cells bind to laminin and destroy basement membrane
- Proteolytic enzymes (collagenase) lyse the Type IV collegen in matrix
- Cells attach to fibronectin in ECM and spread locally
- Tumor cells migrate
cancer of neuroendocrine cells
carcinoid tumor
Heavy metal inhalation
associated with lung cancer
Cancer of plasma cells
Multiple Myeloma
polyp
benign epithelial tumor prodtruding from epithelial surface
Paraneoplastic Syndrome: Hyponatremia
small cell carcinoma of lung; due to ADH
Blood level is high in prostate cancer
Psostatic Acid Phosphatase (PAP), Prostate Specific Antigen (PSA)
Cachexia
loss of body fat, lean body mass, weakness, anorexia, and anemia
Increased metabolism of all nutrients - may involve Cachectin
cancer of hemopoietic cells of bone marrow
Leukemia
Normally produced by embryonal gut, pancreas, liver.
Serum level may be high in colorectal, pancreatic, liver, and gastric cancers.
Carcinoembryonic Antigen (CEA)
UV Rays
squamous cell carcinoma, basal cell carcinoma, malignant melanoma
Aromatic Amines and azo dyes: beta-napthalamine
causes bladder cancer among workers with aniline dye and rubber industry
Keratin (marker)
Epithelium
Retinoblastoma (cause)
Caused by deletion of Rb gene on chromosome 13
Rb is a tumor suppressor
seruos cystadenoma
contains serous fluid
Encapsulation
Peripheral, circumferential fibrous connective tissue rim around benign tumors
Benign tumor of glandular epithelium
Adenoma
Teratoma
benign tumor composed of more than one germ layer, usually all three. Totipotential cells of testis or overy can differentiate along various germ lines
Normally produced by yolk sac and fetal liver. Blood level goes up in cancer of liver and germ cell tumor of testis.
Alpha-fetoprotein (AFP)
When do symptoms from a tumor first occur
after 30 divisions
Paraneoplastic Syndrome: Acanthosis nigricans (dark patches of skin)
gastrointestinal cancer
Stroma
Supporting connective tissue and blood vessels