Exam #2: Neoplasia VI Flashcards
What is the mechanism of UVB tumorigenesis?
- UVB (280-320 nm) causes the formation of pyrimidine dimers
- Pyrimidine dimers cause DNA damage
What is the pathway of DNA repair following UVB damage?
NER pathway i.e. nucleotide excision repair
What is Xeroderma Pigementosum?
This is a condition in which infected individuals have enzyme defect in DNA repair (NER pathway), making the patient highly susceptible to radiation damage
What is ionizing radiation?
Ionizing radiation is radiation with enough energy so that during an interaction with an atom, it can remove tightly bound electrons from the orbit of an atom, causing the atom to become charged or ionized. Types of ionizing radiation include:
- Alpha rays
- Beta rays
- Gamma rays
- Neutrons
- X-ray
Note that alpha, beta, and neutrons are worse than gamma & x-rays; these are particulates
What are the two ways that ionizing radiation can cause DNA damage?
1) Direct effect i.e. direct damage to DNA
2) Indirect effect= free radical generation, which then damage DNA
What are the mechanisms of DNA damage that lead to tumorigenesis in ionizing radiation?
1) Chromosome breakage
2) Translocation
3) Point mutation
What are the most common cancers caused by radiation?
Leukemia, except CLL
Thyroid papillary cancer
Breast/ lung
In response to atomic bomb radiation, is skin cancer likely?
No–skin is most sensitive to UV radiation
What cancers are associated with x-rays workers?
Radiation dermatitis
Skin cancer
For workers that commonly work with radium, what cancer is most common? What occupation is associated with radium exposure?
Osteosarcoma
–This is associated with factory workers that dials of watches that contain “luminous radium”
How do Hepatitis B & C lead to liver cancer?
Chronic liver damage leads to chronic regeneration and regenerative hyperplasia, which can transform to dysplasia & eventually malignancy
B= Hepatitis B also produces HBX protein
- Stimulates insulin-like growth factor
- Binds & inhibits p53
What cancers are associated with EBV?
- Burkitt Lymphoma
- Hodgkin Lymphoma
- B-cell Lymphoma in immunosuppressed patients
- Nasopharyngeal carcinoma
Which subtypes of HPV are associated with cancer? What are the mechanisms of carcinogenesis?
- HPV 16, 18, & 31 are “high risk” b/c they INTEGRATE their DNA into host DNA
- E6= p53 inhibitor
- E7= Rb, p53, & p21 inhibitor
What subtypes of HPV are “low risk” & why?
- HPV 6 & 11 only cause benign tumors
- These subtypes of HPV do NOT integrate into the genome of the host
Not integrated= “episomal”
What is the primary cancer causing RNA virus?
Human T-cell Leukemia Virus Type 1 (HTLV-1)
HTLV-1 is a retrovirus of the human T-lymphotropic virus (HTLV) family that has been implicated in several kinds of diseases including very aggressive adult T-cell lymphoma (ATL)
Where is HTLV-1 endemic?
Japan
Caribbean basin
What is the mode of transmission for HTLV-1?
Intercourse
Blood
Breast feeding
What is the mechanism of HTLV-1?
Virus contains Tax gene that:
1) Stimulates transcription of viral mRNA
2) Activates c-FOS, IL-2, and GM-CSF in the host
- IL-2 is a growth factor for T-cells that is activated by the virus
- c-FOS 7 GM-CSF are both growth factors
3) Inactivates p16INK4a
What is p16INK4a?
Tumor suppressor
What is HHV-8 & what cancer is it associated with?
HHV-8= Human Herpes Virus; this is an HIV-associated virus that leads to the development of Kaposi sarcoma
What are the symptoms of Kaposi Sarcoma?
Red-purple macules, papules, or nodules
What tumors are associated with H. pylori infection?
1) Gastric carcinoma
2) Gastric Lymphoma (MALT)
How does H. pylori cause cancer?
H. pylori encodes CagA (Cytotoxin associated gene A), which is a toxin stimulates growth factor pathways
What hormones are carcinogeneic?
Estrogen
Contraceptive hormones
Anabolic steroids
What cancers is estrogen associated with?
First, remember that estrogen can BOTH initiate AND promote cancer
- Breast
- Squamous cell carcinoma of the cervix
- Leiomyoma of uterus
What are the contraceptive hormones associated with?
- Breast cancer
- Benign/malignant liver tumors
What cancers are associated with anabolic steroids?
Benign & malignant liver tumors
What are the three general clinical manifestations in a patient with a tumor?
1) Local or hormonal effects
2) Cancer cachexia
3) Para-neoplasic syndrome
What is cancer cachexia & what causes cancer cachexia?
Loss of body fat, wasting & profound weakness; caused by loss of appetite, metabolic changes, and TNF-a
The key point here is TNF-a
What are para-neoplastic syndromes?
Distant effects of a tumor unrelated to the primary tumor or metastasis i.e. the tumor produces a hormone; that hormone secretes in the body and has a generalized effect
*****Note that this may represent the earliest manifestation of a cancer
List examples of para-neoplastic syndromes.
1) ACTH/ Cushing Syndrome
2) SIADH/ hyponatremia
3) Acanthosis nigricans
What cancer is SIADH associated with? What does SIADH lead to & why?
Small cell carcinoma of the lung
- Tumor secretes ADH
- Causes water retention
- Leads to dilution of Na+ in the blood
What is Acnathosis nigricans? What cancer is this associated with?
- This is a black, verrucoid appearing lesion in the skin, usually the axilla
- Gastric carcinoma
What is the second skin lesion associated with gastric carcinoma?
Lesser-Trelat sign
**This is an explosive onset of multiple seborrheic keratoses[1] (many pigmented skin lesions), often with an inflammatory base
What is Carcinoid Syndrome? What cancers is this associated with?
- This is a syndrome associated with neuroendocrine tumors
- Tumor is located in the appendix or small intestine & overproduces 5-HT
- Causes flushing, diarrhea, bronchospasm and tachycardia esp. on palpation of the abdomen
How is Carcinoid Syndrome diagnosed?
Urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) –a metabolite of 5-HT
What is the cause of nearly 40% of all clinical cases of hypercalcemia?
Malignancy
What are the causes of hypercalcemia in malignancy?
1) Release of PTH-like peptide
2) Osteolytic effect of bony metastasis
- Breast cancer
**Note that breast cancer can also have osteoblastic effects as well
What cancers are associated with the release of PTH?
- Squamous cell carcinoma of the lung
- Renal cell carcinoma
*****Note that these patients may have LOW levels of PTH; PTH-like peptide is causing the symptoms, NOT PTH, & Ca++ has a negative feedback on PTH
What causes hypocalcemia seen in cancer? What cancers is hypocalcemia associated with?
Medullary cancer of the thyroid
- Tumor releases calcitonin
What cancer is associated with gynecomastia? What hormone is causing gynecomastia?
Choriocarcinoma of the testis
- B-HCG
What is Eaton-Lambert Syndrome? What cancer is associated with Eaton-Lambert Syndrome?
Eaton Lambert Syndrome is a Myasthenia Gravis-like syndrome i.e. neuromuscular disease that leads to fluctuating muscle weakness and fatigue
- Eaton Lambert Syndrome is associated with Small Cell Cancer of the Lungs
What are the three general methods for diagnosing cancer?
1) Morphology
2) Molecular methods
3) Biochemical assay i.e. tumor markers
What are the different techniques used for morphological diagnosis of cancer?
Biopsy Frozen section FNAC--Fine needle aspiration cytology Cytology IHC
What are the molecular methods used for cancer diagnosis?
Flow cytometry
DNA probe analysis
When should you use immunohistochemistry (IHC) for cancer diagnosis?
- Diagnosis of undifferentiated tumors i.e. this is how you find the origin
- Categorization of leukemias and lymphomas
How would you know that a tumor is epithelial in origin (marker)?
Positive for cytokeratin or EMA i.e. epithelial membrane antigen
How would you know that a tumor is mesenchymal in origin?
Vimentin
What does desmin positive marker tell you?
Muscle specific origin
What is LCA? What does an LCA positive tumor indicate?
Leukocyte common antigen
- Leukocyte origin
What are the three markers associated with neuronal tumors?
1) Neuron-specific enolase
2) Chromogranin
3) Synaptophysin
What types of tumors aside from strictly neuronal tumors will be positive for the marker, NSE?
Neuroendocrine tumors e.g.
- Small cell carcinoma of the lung
- Carcinoids
What is Thyroglobulin a marker for?
Thyroid cancer
What is CD10 (CALLA) a marker for?
Acute Lymphoblastic Leukemia (ALL)
What is Placental Alkaline Phosphatase a marker for?
Seminoma i.e. germ-cell tumor of the testicles
What are vWF & CD31 markers for?
Vascular neoplasms
What is a tumor marker?
Substance found in the blood, urine, or body tissue that can be elevated in cancer
What is CEA? What is this a tumor marker for?
CEA= Carino-embryonic antigen that is a tumor marker for:
- Colon
- Pancreas
- Stomach
- Breast*
What is PSA & what is PSA a marker for?
PSA= Prostate-Specific Antigen, which is a tumor marker for prostate cancer
What is B-HCG? What is B-HCG a marker for?
B-HCG= beta-Human Chorionic Gonadotropin, which is a tumor marker for trophoblastic tumors i.e. choriocarcinoma
What is CA-125 a tumor marker for?
Ovarian carcinoma
What is AFP? What is AFP a tumor marker for?
AFP= alpha-fetoprotein, which is a tumor marker for
- Heptaocellular carcinomas
- Germ cell tumors of testes or ovaries
What is NSE a tumor marker for?
Small cell carcinoma of the lung
What is calcitonin a tumor marker for?
Medullary thyroid carcinoma
What is CA 19-9 a tumor marker for?
Colon & pancreatic cancer
What is CA 15-3 a tumor marker for?
Breast carcinoma
