Oncogenes, Carcinogens, Tumor Markers/Stains, Paraneoplastic Syndromes Flashcards
ALK
proto-oncogene; tyrosine kinase receptor
lung adenocarcinoma
EGFR (ERBB1)
proto-oncogene; epidermal growth factor (EGFR; ERBB1; HER1 in humans); receptor tyrosine kinase
lung adenocarcinoma
HER2 (ERBB2)
proto-oncogene; receptor tyrosine kinase
breast and gastric carcinomas
RET
proto-oncogene; receptor tyrosine kinase
MEN2A and 2B, medullary and papillary thyroid carcinoma, pheochromocytoma
BCR-ABL
proto-oncogene; non-receptor tyrosine kinase
CML, ALL
JAK2
proto-oncogene; non-receptor tyrosine kinase
myeloproliferative neoplasms
BRAF
serine/threonine kinase
melanoma, non-Hodgkin lymphoma, colorectal carcinoma, papillary thyroid carcinoma, hairy cell leukemia
c-KIT
proto-oncogene; cytokine receptor (CD117)
gastrointestinal stromal tumor (GIST), mastocytosis
MYCC (c-myc)
proto-oncogene; transcription factor
Burkitt lymphoma
MYCN (n-myc)
proto-oncogene; transcription factor
neuroblastoma
KRAS
proto-oncogene; RAS GTPase
colorectal, lung, pancreatic cancers
BCL-2
proto-oncogene; antiapoptotic molecule
follicular and diffuse large B cell lymphoma
APC
tumor suppressor gene; negative regulator of beta-catenin/WNT pathway
colorectal cancer (FAP)
BRCA1/BRCA2
tumor suppressor gene; BRCA1/BRCA2 proteins
breast, ovarian, prostate, pancreatic cancer
CDKN2A
tumor suppressor gene; p16, blocks G1 -> S phase
many cancers (melanoma, lung, pancreas)
DCC
tumor suppressor gene; DCC gene
colorectal cancer
SMAD4 (DPC4)
tumor suppressor gene; DPC gene
pancreatic cancer, colorectal cancer
MEN1
tumor suppressor gene; menin
multiple endocrine neoplasia type 1
NF1
tumor suppressor gene; neurofibromin (RAS GTPase activating protein)
neurofibromatosis type 1
NF2
tumor suppressor gene; merlin (schwannomin) protein
neurofibromatosis type 2
PTEN
tumor suppressor gene; negative regulator of PI3k/AKT pathway
prostate, breast, and endometrial cancers
RB1
tumor suppressor gene; inhibits EF2 (blocks G1 -> S phase)
retinoblastoma, osteosarcoma
TP53
tumor suppressor gene; p53 activates p21, which blocks G1 -> S phase
most cancers, Li-Fraumeni syndrome
TSC1
tumor suppressor gene; hamartin protein
tuberous sclerosis
TSC2
tumor suppressor gene; tuberin
tuberous sclerosis
VHL
tumor suppressor gene; inhibits hypoxia-inducible factor 1a
von Hippel-Lindau disease
WT1
tumor suppressor gene; urogenital development transcription factor
Wilms tumor (nephroblastoma)
aflatoxins
from Aspergillus; stored grains and nuts
hepatocellular carcinoma
alkylating agents
oncologic chemotherapy
leukemia/lymphoma
aromatic amines (benzidine, 2-naphthylamine)
textile industry (dyes), tobacco smoke (2-naphthylamine)
transitional cell carcinoma
arsenic
herbicides (vineyard workers), metal smelting, wood preservation
hepatic angiosarcoma, lung cancer, squamous cell carcinoma (skin)
asbestos
old roofing material, shipyard workers
bronchogenic carcinoma > mesothelioma
tobacco smoke
transitional cell carcinoma (bladder), squamous cell carcinoma (cervix, esophagus, larynx, lung, oropharynx), esophagus adenocarcinoma, renal cell carcinoma, small cell lung cancer, pancreatic adenocarcinoma
ethanol
esophagus squamous cell carcinoma, hepatocellular carcinoma, breast cancer
ionizing radiation
leukemia, papillary thyroid carcinoma
nickel, chromium, beryllium, silica
occupational exposure
lung cancer
nitrosamines
smoked foods
gastric cancer (intestinal type)
radon
byproduct of uranium decay, accumulates in basements
lung cancer (2nd leading cause after tobacco smoke)
vinyl chloride
used to make PVC pipes
hepatic angiosarcoma
serum tumor marker: alkaline phosphate
metastases to bone or liver, Paget disease of bone, seminoma
serum tumor marker: alpha-fetoprotein
hepatocellular carcinoma, endodermal sinus (yolk sac) tumor, mixed germ cell tumor, ataxia-telangiectasia
in pregnancy, high levels associated with neural tube and abdominal wall defects, low levels associated with Down syndrome
serum tumor marker: hCG
hydatidiform moles and choriocarcinomas (gestational trophoblastic disease), testicular cancer, mixed germ cell tumor
serum tumor marker: CA 15-3/ CA 27-29
breast cancer
serum tumor marker: CA 19-9
pancreatic adenocarcinoma
serum tumor marker: CA 125
epithelial ovarian cancer
serum tumor marker: calcitonin
medullary thyroid carcinoma (alone and in MEN2A, MEN2B)
serum tumor marker: CEA
colorectal and pancreatic cancers
serum tumor marker: chromogranin
neuroendocrine tumors
serum tumor marker: LDH
testicular germ cell tumors, ovarian dysgerminoma
serum tumor marker: neuron-specific enolase
neuroendocrine tumors (small cell lung cancer, carcinoid tumor, neuroblastoma)
serum tumor marker: PSA
prostate cancer
IHC stains: chromogranin and synaptophysin
target: neuroendocrine cells
small cell carcinoma of the lung, carcinoid tumor, neuroblastoma
IHC stains: cytokeratin
target: epithelial cells
epithelial tumors (squamous cell carcinoma)
IHC stains: desmin
target: muscle
muscle tumors (rhabdomyosarcoma)
IHC stains: GFAP
target: neuroglia (astrocytes, Schwann cells, oligodendrocytes)
astrocytoma, glioblastoma
IHC stains: neurofilament
target: neurons
neuronal tumors (neuroblastoma)
IHC stains: PSA
target: prostatic epithelium
prostate cancer
IHC stains: S-100
target: neural crest cells
melanoma, schwannoma, Langerhans cell histiocytosis
IHC stains: TRAP
target: tartrate-resistant acid phosphatase
hairy cell leukemia
IHC stains: vimentin
target: mesenchymal tissue (fibroblasts, endothelial cells, macrophages)
mesenchymal tumors (sarcoma); also many other tumors (endometrial carcinoma, renal cell carcinoma, meningioma)
psammoma bodies are found in [?]
“PSAMMOMaS”:
Papillary carcinoma of thyroid
Somatostatinoma
Adrenals (calcifying fibrous pseudotumor)
Meningioma
malignant Mesothelioma
Ovarian serous carcinoma
prolactinoma (Milk)
Serous endometrial carcinoma
dermatomyositis
progressive proximal muscle weakness, Gottron papules, heliotrope rash
adenocarcinomas, especially ovarian
acanthosis nigricans
hyperpigmented velvety plaques in axilla and neck
gastric adenocarcinoma and other visceral malignancies
sign of Leser-Trelat
sudden onset of multiple seborrheic keratoses
GI adenocarcinomas and other visceral malignancies
hypertrophic osteoarthropathy
abnormal proliferation of skin and bone at distal extremities => clubbing, arthralgia, joint effusions, periostosis of tubular bones
adenocarcinoma of the lung
hypercalcemia
PTHrP: squamous cell carcinomas of lung, head, and neck; renal, bladder, breast, and ovarian carcinomas
increased 1,25-(OH)2 vitamin D3 (calcitriol): lymphoma
Cushing syndrome
increased ACTH
small cell lung cancer
hyponatremia (SIADH)
increased ADH
small cell lung cancer
polycythemia
increased erythropoietin
Pheochromocytoma, Renal cell carcinoma, Hepatocellular carcinoma, Hemangioblastoma, Leiomyoma
“Paraneoplastic Rise to High Hematocrit Levels”
pure red cell aplasia
anemia with low reticulocytes
thymoma
Good syndrome
hypogammaglobulinemia
thymoma
Trousseau syndrome
migratory superficial thrombophlebitis
adenocarcinoma, especially pancreatic
nonbacterial thrombotic endocarditis
deposition of sterile platelet thrombi on heart valves
adenocarcinoma, especially pancreatic
anti-NMDA receptor encephalitis
psychiatric disturbance, memory deficits, seizures, dyskinesias, autonomic instability, language dysfunction
ovarian teratoma
opsoclonus-myoclonus ataxia syndrome
“dancing eyes, dancing feet”
neuroblastoma (children), small cell lung cancer (adults)
paraneoplastic cerebellar degeneration
antibodies against antigens in Purkinje cells
small cell lung cancer (anti-Hu), gynecologic and breast cancers (anti-Yo), and Hodgkin lymphoma (anti-Tr)
paraneoplastic encephalomyelitis
antibodies against Hu antigens in neurons
small cell lung cancer
Lambert-Eaton myasthenic syndrome
antibodies against presynaptic calcium channels at neuromuscular junction
small cell lung cancer
myasthenia gravis
antibodies against postsynaptic ACh receptors at neuromuscular junction
thymoma
t(8;14)
Burkitt lymphoma (c-myc activation)
t(11;14)
mantle cell lymphoma (cyclin D1 activation)
t(11;18)
marginal zone lymphoma
t(14;18)
follicular zone lymphoma (BCL-2 activation)
t(15;17)
APL (formerly AML type M3)
t(9;22)
Philadelphia chromosome; CML (BCR-ABL hybrid), less commonly ALL