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Oncology

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Oncology

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  1. Oncology Dan Cushman

  2. Cancer No presence detected by any currently available studies What is “complete remission?” Decrease in tumor size by 50% What is “partial remission?” Obtain a piece of the tumor (not the whole thing) What is an incisional biopsy? Lung, breast, colon What are the main three cancers in terms of mortality? Age Main risk factor for cancer? Smoking #2 risk factor? Breast, bone, thyroid Three most sensitive tissues to oncogenic exposure? Tissue What is the issue?

  3. Epidemiology of Cancer 1.5 million How many incidences of cancer in the US annually? 1:3 What is the lifetime risk of developing cancer? They’re both decreasing Are incidences and mortality rates of cancer increasing or decreasing? Men Who has a higher mortality rate – men or women? Prostate, Lung, Colorectal Top three male cancers? Breast, lung, uterus Top three female cancers? Lung, prostate, colorectal Top three male cancers in terms of mortality? Lung, breast, colorectal Top three female cancers in terms of mortality?

  4. Epidemiology of Cancer Leukemia, CNS, lymphoma Main three pediatric cancer sites? Tobacco, diet, infectious processes Top three environmental risk factors for cancer? Smoking isn’t cool Mammogram, PSA, sigmoidoscopy, PAP smear Four main screening programs for cancer? 30% What percentage of cancer deaths are caused by smoking? Lung, oropharyngeal, esophageal, pancreatic, bladder, laryngeal, renal, cervical, colorectal, … Which cancers are caused by smoking?

  5. Molecular Biology The inactive trimer dissociates into an α- and a β/γ subunit; the α subunit binds GTP What happens to a G-protein upon activation? The GTP of the active α subunit is hydrolyzed upon binding to a target protein How are G proteins inactivated? Joke of the day G-protein-coupled reaction  increase in cAMP What does a β-adrenergic receptor do after a ligand binds (step 1) ? Activates PKA The increased cAMP does what? Q: What does the molecular biologist do for fun? What does PKA then do? Enters the nucleus and promotes cell cycle progress & DNA replication by using the CREB protein A1: They go cAMPing. How is Ras activated? A receptor tyrosine kinase (RTK) allows Ras to trade its GDP for a GTP A2: Let’s be realistic, molecular biologists are never fun. Activates the kinase cascade What does the activated Ras protein do next? Activates transcription factors, resulting in the stimulation of DNA synthesis and cell division (e.g. myc) What does the kinase cascade eventually do?

  6. Molecular Biology G-proteins, RTK, PIP3 How is PLC activated? PIP2 What molecule does PLC work on? Diacylglycerol (DAG) + Inositol triphosphate (IP3) What is created when PLC cleaves PIP2? IP3 IP3-gated Calcium channels  increase in intracellular [Ca]  activates PKC + CalmodulinKinase What does the IP3 end up doing? DAG directly activates PKC What does the DAG lead to? PKC enters the nucleus and promotes cell cycle progression. It also activates the kinase cascade. What does PKC do? PI 3-kinase What is an alternate enzyme that works on PIP2? Both RTKs and G-protein-linked receptors How is PI 3-kinase activated?

  7. Molecular Biology PIP3 What does PI 3-kinase create from PIP2? It activates other cell division and metabolism pathways (e.g. PLC-γ, PKB, PKC) …and what does PIP3 do? It inhibits apoptosis What does PKB ultimately do? PKB  BCL-2  inhibits apoptosis What intermediate molecule accomplishes this? PKB  mTOR Through what other mechanism can PKB affect cell growth? Rapamycin (mTOR = “mammalian Target of Rapamycin”) What drug can block mTOR? Promotion of the cell cycle What does WNT ultimately cause? WNT   Blocks APC  frees β-catenin transcription What is the pathway for WNT?

  8. Molecular Biology APC generally “mops up” excess β-catenin in the cell, preventing cell cycle progression What is the relationship between APC and β-catenin? Metastasis (↑ Wnt ↓ e-cadherins cell migration) and invasion (↑ metalloproteinases) What other aspect of cancer is Wnt responsible for? Transforming growth factor What does TGF stand for? Epithelial cells = tumor suppressor, mesenchymal = stimulatory How does TGF behave for mesenchymal and epithelial cells? Smad What intermediate molecule is part of the TGF-β pathway in epithelial cells? Chronic myelogenous leukemia What is Gleevec used for? It replaces ATP in the bcr-ablprotein How does Gleevec work? PTEN phosphatase What inhibits PI 3-kinase activity?

  9. Molecular Biology

  10. Steps…

  11. Molecular Biology E2F To which molecule is Rb normally bound? What activates Rb? Cyclin D : CDK4/6 Cyclin E: CDK2 Tip of the day Cyclin D : CDK4/6, plus the positive feedback loop created by CDK2 : Cyclin E What is required for E2F to initiate DNA replication factors? p21 (p53) and p27 What inhibits CDK2 : Cyclin E? No matter how cool you think you are, never say “Cyclin-dependent kinase” at a dinner party. DNA damage What activates ATM? Activates p53 Activated ATM does what? Never. Mdm2(which binds p53) is blocked by ATM How is p53 activated by ATM? Upregulates DNA repair enzymes (BRCA, chk) What else does ATM do?

  12. Molecular Biology It ubiquitinatesp53 What is the purpose of Mdm2? Multiple stages At which point of the cell cycle can ATM be activated? Deep thought of the day Both – oncogenic in response to growth factors, suppressive in high levels Is myc oncogenic or tumor suppressing? How does myc relate to p53? mycp14ARFp53 If you were a Fas ligand, would you be proud of your job? How can myc be oncogenic? It is a powerful transcription factor for multiple genes (cyclin D, E2F, p27 degradation) TGF-β p16INK4; TGF-β  p27  inhibits CDK2 : Cyclin E How does TGF-β inhibit the cell cycle? It is inhibitory to p16 How else can myc be oncogenic? Fas ligand  Fas protein  caspase cascade  apoptosis What is the extrinsic pathway of apoptosis activation?

  13. Molecular Biology Mitochondria What is the main cell organelle involved in the intrinsic pathway of apoptosis activation? Cytochrome C What is released from the mitochondria to trigger apoptosis? Bax(from p53) What protein initiates the release of cytochrome C from the mitochondria? BCL-2 What protein inhibits cytochrome C release? They overexpressBCL-2 What is the probable relation between breast tumors and BCL-2? The ends become sticky  chromosome fusion and breakage What happens to chromosomes that lack telomerases? Usually not, unless there is a concurrent loss of p53 Will a lack of telomeres result in the breakage-fusion-breakage cycle? It ubiquinates proteins for degradation in proteosomes What is the main (general) function of APC?

  14. Molecular Biology CDK4/6 : Cyclin D, followed by CDK2 : Cyclin E What cyclins and CDKs are involved in progressing a cell from the G1 phase to the S? CDK2 : Cyclin A What cyclins and CDKs are involved in progressing a cell from the S phase to the G2? CDK1 : Cyclin B What cyclins and CDKs are involved in progressing a cell up to the mitosis phase? Metaphase Up to which phase of mitosis does the CDK1 : Cyclin B combination work? The destruction of cyclin B (and inactivation of CDK1) by APC What event allows for the initiation of anaphase? APC (Adenomatous Polyposis Coli) Which protein is often responsible for starting the transition to cancer in patients with Familial Polyposis Coli? TGF-β is knocked out Which protein is often responsible for starting the transition to cancer in patients with HNPCC? DNA repair enzymes, helped by p53 What are the functions of the BRCA1 & 2 genes (associated with breast cancer)?

  15. Molecular Biology Ras, but myc + Ras is far more oncogenic Which induces more tumors – myc or Ras? Dominant Are oncogenes dominant or recessive? Recessive Are tumor suppressors dominant or recessive? Single point mutation hyperactive protein made in normal amounts What is the usual mechanism for the development of a mutation in the Ras protein? Gene amplification normal protein greatly overproduced What is the usual mechanism for the development of a mutation in the N-mycprotein? Chromosomal rearrangement What is the usual mechanism for the development of a mutation in the abl protein? It is a key feature of the ability of a cell to metastasize What is important about the ability of a cell to undergo epithelial-to-mesenchymal transition? It is resistant to chemotherapy (due to its quiescence) and it is able to reseed new tumors after treatment If a stem cell gives rise to and perpetuates a tumor, why is this dangerous?

  16. Pathology Loss of responsiveness to normal growth controls What characterizes a neoplasm? Sarcoma What is the term given to a malignant tumor of mesenchymal origin? Carcinomas Which is more common – carcinomas or sarcomas? HTLV-1, EBV, HBV, HPV Name four oncogenic viruses 16 & 18 Which strains of HPV are oncogenic? It refers to the level of cytologic differentiation What is “grading?” It takes into account the lesion size, extent of spread, and presence of metastases What is “staging?” Tumor suppressors Which are related to the “two-hit” hypothesis – tumor suppressors or oncogenes?

  17. Immune System After resecting a tumor from a mouse, injection of tumor cells back into the “cured” mouse resulted in no tumor What animal-based experiment showed a role of the immune system in tumor control? Mutation  new protein  new Ag; Overexpression of normal self-protein  increased density of Ag What are the two ways in which a tumor can be recognized by the immune system? Dendritic cells, macrophages, and B cells What are the three types of professional antigen-presenting cells? Both Which is involved in tumor detection and destruction – the innate or the humoral immune system? Both (immunoediting) Does the immune system help limit or facilitate tumor growth? Elimination, equilibrium, and escape What are the three elements of immunoediting? Low immunogenicity, antigenic modulation, and tumor-induced immune suppression What are three mechanisms in which tumors escape immune recognition? Incubation of tumor-based lymphocytes with IL-2  injection back into patient How can IL-2 be used to fight cancer?

  18. Cell Cycle Cdk1-cyclinB CDK?:Cyclin? 4 Cdk4-cyclin D Cdk6-cyclin D 1 CDK?:Cyclin? Cdk2-cyclin A 3 CDK?:Cyclin? 2 Cdk2-cyclin E CDK?:Cyclin?

  19. Which portion of the cycle involves the replication of the DNA genome? Which portion of the cycle involves nuclear and cytoplasmic division? Which portion of the cycle involves the synthesis of cellular components for mitosis? Which portion of the cycle involves the synthesis of cellular components for DNA synthesis? Cell Cycle

  20. Oncological Surgery Resectability refers to the ability to remove the tumor, while operability refers to the overall condition of the patient What is the difference between “operable” and “resectable?” Colon Which type of cancer can metastasize and still be treated surgically? Liver > Lung Where does colon cancer generally metastasize? Don’t cut into the tumor, as it can seed other tissues During surgery, where should the surgeon avoid cutting? After; neoadjuvant is given before Is adjuvant chemotherapy given before or after surgery? Yes Is surgery appropriate for palliation? Reconstructive Apart from palliation, when else would surgery be used for non-curative oncologic means?

  21. Radiation Oncology Radiosensitivity refers to ability of the cell to respond to radiotherapy, not necessarily its ability to be completely eliminated What is the difference between “radiocurability” and “radiosensitivity?” An implantable device that gives localized radiation What is brachytherapy? Acute < 3 months Subacute3-6 months Chronic >6 months What length of time signifies acute radiation damage? Subacute? Chronic? Highly-active cells (high growth rate) What type of cells are most susceptible to X-ray-induced damage? S phase (G0 phase too?) Which stage of the cell cycle is least susceptible to DNA damage from X-rays?

  22. Chemotherapy Rapidly-dividing tissue (hair, bone marrow, GI tract, gonads, etc.) Which normal tissues are most often affected by chemotherapy? No; they differentiate between rapidly-dividing and slow- or non-dividing cells Can chemotherapeutics differentiate between normal and cancerous cells? Tip of the day A percentage of cells is killed with each treatment; starting with a smaller tumor has a better chance of being completely eliminated What’s the “Log Kill Hypothesis?” What is the equation for the growth fraction? Cells in G1, S, G2, & M ------------------------------------ Cells in G0, G1, S, G2, & M Don’t try to make a joke about chemotherapy. You can’t win that one. Which is more difficult to treat – a higher or lower growth fraction? Lower, because less cells are cycling Neither; non-phase-specific agents kill cells in G1, G2, S, or M Which kills cells in G0… phase-specific or non-phase-specific agents? Transporters, block apoptosis, slow-growing cells (hypoxia) Name the three methods of resistance-development for tumors Hypoxic cells have less ability to generate ATP from oxidative processes and depend more on glycloysis How can inhibiting glycolysis kill tumor cells?

  23. Antimetabolites Yes Phase-specific? S-phase Which phase? Tip of the day Mercaptopurine, methotrexate, ARA-C Name three main drugs in the class Block synthesis of replication metabolites – mostly DNA or RNA building blocks Mechanism of action? Can’t remember how mercaptopurine works? How does methotrexate work? Binds DihydrofolateReductase inhibits formation of purines Just remember that “mercapto” is Latin for “wanna-be” How does mercaptopurine work? It’s a purine analog For example, you could say some people are “mercaptosexy” or “mercaptoblack” Decreased polyglutamate (which traps methotrexate in the cell) How can cells become resistant to methotrexate? Mercaptopurine (it’s usually inactivated by xanthineoxidase, which is blocked by allopurinol) Which antimetabolite has a dangerous interaction with allopurinol?

  24. Alkylating Agents No Phase-specific? They are metabolized by the liver, which activates them What is important about their metabolism? Mustards,Cyclophosphamide, Chlorambucil Name three main drugs in the class Alkylate DNA  DNA damage Mechanism of action? AldehydeDehydrogenase (low levels in tumor cells  higher potency) Which enzyme helps degrade cyclophosphamide? Brain tumors (they’re highly lipophilic and can cross the BBB) Where are nitrosoureas (chlorambucil, melphalan) useful?

  25. Anthracyclines No Phase-specific? Cardiac Main toxicity? Adriamycin, doxorubicin Name two main drugs in the class Intercalate into DNA block transcription Mechanism of action? It is cumulative What is special about the cardiac toxicity?

  26. Tubulin-Binding Agents Yes Phase-specific? M-phase Which phase? Taxol, vinca alkaloids Name the main drugs in the class Impairs proper microtubule formation Mechanism of action? Neurotoxicity (remember that synaptic vesicles are carried on microtubules) What is the main form of toxicity for these agents?

  27. Chemotherapy Toxicities

  28. Chemotherapy Using two drugs with different mechanisms that function additively What is “therapeutic synergism?” It can shrink the tumor, making it easier to resect; the patient is healthier pre-surgery; sensitivity to a specific drug can be monitored What are the advantages of using a neoadjuvant? Bind ligand Bind receptor Inhibit kinase activity Inhibit secondary messengers What are the four ways with which signal transduction can be interfered? Tumor cells often create excess proteins, which can overwhelm cell if they are not degraded How can a proteosome inhibitor be useful for tumor cells? CML For which type of cancer is Gleevec used? A RTK that receives epidermal growth factor (EGF) What is the HER receptor?

  29. Monoclonal antibodies Non-Hodgkin Lymphoma What is Rituximab used for? CD20 on B-lymphocytes …what does it target? Factoid of the Day 80%, but tend to improve after first infusion How common are side effects with Rituximab? What is Trastuzumab (Herceptin) used for? Metastatic breast cancer Monoclonal antibodies are named after their founder. HER2 membrane protein …what does it target? Guess who developed Rituximab? Is it useful in all breast cancers? 25% of patients express amplified amounts of HER2 protein Hint: her last name is Gupta. Fever/chills, pain at the tumor site, GI, cardiac dysfunction What are the side effects?

  30. Paraneoplastic Syndromes Immune-mediated, hormone-mediated, thrombophilia What are the three general types of paraneoplastic syndromes? Antibodies against voltage-gated Calcium channels at the NMJ What is the pathophysiology of Lambert-Eaton Syndrome? Small-cell cancer of the lung To which type of cancer is LES classically related? Proximalmuscles of the lower extremities Where does LES usually present itself? It is cytokine-mediated and caused by a malignancy Why is cachexia considered a paraneoplastic syndrome? Involuntary loss of >5% of body weight What is the definition of cachexia? Cachexia is a hypermetabolic state that can not be overcome by eating more What is the difference between anorexia and cachexia? GI and lung cancers Which two general types of cancer are most commonly associated with cachexia?

  31. Paraneoplastic Syndromes Increased lipolysis, proteolysis  skeletal muscle loss, neurologic symptoms What is affected in states of cachexia? TNF-α, IL-1, IL-6, PTHrP What are the main cytokines associated with cachexia (4)? Steroids, dronabinol, marijuana How can cachexia be treated? Dermatomyositis Which type of paraneoplastic syndrome gives fever, fatigue, proximal weakness, and a rash? Creatinekinase What lab is elevated in dermatomyositis? Treat cancer; steroids How do you treat dermatomyositis? Hypercalcemia What is the most common paraneoplastic electrolyte imbalance? Humoral(PTHrP or calcitriol production), Osteolytic What causes the hypercalcemia (2)?

  32. Paraneoplastic Syndromes Fatigue, weakness, constipation, altered mental status, polyuria, decreased QT interval What are the main symptoms of hypercalcemia? Neuroendocrine tumors (carcinoid, pancreatic NE tumor) Which types of cancer are associated with Cushing’s Syndrome? ↓[Na] due to ↑ADH production (from tumor) What causes paraneoplastic hyponatremia? Poor If a clotting disorder is the first sign of a cancer, what is the prognosis? Hypercoagulable Cancer – hyper- or hypocoagulable? Fluids and bisphosphonates How is hypercalcemia treated? Heparin, not coumadin What drug should be used for avoiding complications of hypercoagulability associated with a malignancy?

  33. Oncologic Emergencies Breast, lung, prostate, kidney Which tumors most commonly cause spinal cord compressions? Yes, it occurs in 20% of vertebral column mets Is spinal cord compression a common paraneoplastic syndrome? Most of those who walk in will walk out, regardless of the cancer Can patients recover after surgery for spinal cord damage? Prompt application of high-dose corticosteroids What’s the treatment for spinal cord compression? Melanoma, lung, breast What types of metastatic tumors are most commonly found in the brain? Solitary = neurosurgery; Multiple = irradiation,steroids How are metastatic brain tumors treated? Lung, breast, melanoma What are the three most common tumors to metastasize to the pleura? The tumor compresses the SVC What is the pathophysiology of SVC syndrome?

  34. Oncologic Emergencies Lung cancer > lymphoma > benign What cancer is the most common cause of the SVC syndrome? The diagnosis is more important than urgent therapy; the tumor is treated appropriately How is SVC syndrome treated? <500 What is the neutrophil count in a neutropenic patient? 7-10 days post-chemo At what stage of chemotherapy is a patient most at risk of developing neutropenia? Bacteria from intestinal flora (E. coli or Pseudomonas) What type of bacteria is a febrile neutropenic patient most likely infected with? Elevated potassium, phosphate, & uric acid; Decreased [Ca] What are the electrolyte imbalances of a patient with tumor lysis syndrome? Allopurinol, hydration What is the treatment for tumor lysis syndrome? Cardiac arrest, electrolyte imbalances, acute renal failure, arrhythmias, hypotension What are the clinical features of tumor lysis syndrome?

  35. Breast Cancer Main two types? Invasive Non-Invasive Lobular Carcinoma Ductal Carcinoma Ductal Carcinoma In-Situ Lobular Carcinoma In-Situ Low-grade High-grade Low-grade High-grade

  36. Breast Cancer 90% benign Are most breast tumors benign or malignant? Yes, most types Is fibrocystic change known to progress to malignancy? Atypical intraductal hyperplasia > intraductal hyperplasia, ductalpapillomatosis Which type of fibrocystic change is most likely to progress to malignancy? Fibroadenomas; they can be sarcomatous What are phyllodes tumors similar to? Phyllodes tumors have increased stromalcellularity What separates a phyllodes tumor from a fibroadenoma, histologically? Bloody discharge from the nipple What is the main presenting sign of a intraductalpapilloma? Well-differentiated Are low-grade tumors well- or poorly-differentiated? Hyperplasia looks very similar to and can progress to CIS What is the relationship between hyperplasia and carcinoma in-situ?

  37. Breast Cancer Cancerous cells pass through ducts all the way to the skin What is the pathophysiology of Paget’s disease? Usually a non-invasive cancer (often DCIS) Is Paget’s disease an invasive or a non-invasive cancer? 60-70% of breast carcinomas express them Is it more common to have a tumor with or without extra estrogen receptors? Tubular, colloid, papillary, and lobular Which tumor types are always ER+? Worse Does overexpression of HER2 give a better or worse prognosis? Herceptin (Anti-HER2 monoclonal antibody) What is the treatment for tumors that overexpress HER2?

  38. Lung Cancer Smoking  metaplasia of bronchial epithelium  dysplasia of squamous epithelium  SCC What is the progression in the development of squamous cell carcinoma? 79% non-small cell Which are more common – small cell or non-small cell carcinomas? Adenocarcinoma, squamous cell > large cell, adenosquamous What are the two most common non-small cell carcinomas? Small Cell Carcinoma Which lung tumors are treated by chemotherapy as the first-line treatment? They contain mucin in the cytoplasm How can adenocarcinomas be identified by histology? Peripheral Are adenocarcinomas found centrally or peripherally? The normal alveolar tissue is lined with malignant cells What is indicative of bronchioalveolar carcinoma, histologically? Typical carcinoid > atypical carcinoid > small cell/large cell Which type of neuroendocrine tumor of the lung carries the best prognosis?

  39. Lung Cancer Endobronchial growth pattern, abundant blood vessels Bronchoscopically, what do carcinoid tumors look like? <45 years old What age group is affected by carcinoid tumors? Metastatic Which is more common in the lung – primary or metastatic tumors? Metastatic Which is more common in the pleura – primary or metastatic tumors? Calretinin (+), Membranous EMA (+) What tumor markers can be found from malignant mesothelioma?

  40. GI Tumors Only 1% of all GI malignancies How common are malignancies of the small intestine? Near the ampulla of Vater Where do most small intestinal adenocarcinomas occur? Epithelial cells in the crypts From what type of tissue are carcinoids of the small intestine derived? Carcinoid of the appendix (it rarely metastasizes, even with local spread) If you had to have one type of GI cancer, what would it be? Serotonin What substance is responsible for the carcinoid syndrome? Interstitial cells of Cajal From what type of cell do gastrointestinal stromal tumors originate? Anywhere in the digestive tract Where do GISTs occur? Gleevec How is GIST treated?

  41. GI Tumors Oh yeah – 40-50% of all people over 60yo have them Are adenomas of the colon common? Tubular > TV > Villous, flat What is the most common type of adenoma? 10 years How long does it take for an adenoma to double in size? Villous > tubular (especially large ones) Which types of adenomas carry a malignant risk? Adenomas progressinto carcinomas over time What is the relationship between adenomas and carcinomas of the colon? Sporadic What is the most common cause of colorectal carcinoma? 60-79yo (<20% are under 50) What age group is most commonly affected by sporadic colorectal carcinoma? Ascending, sigmoid Which sections of the colon are most commonly affected by sporadic CC?

  42. GI Tumors Lung, liver, bone To where do colorectal carcinomas usually metastasize? Mucosal/cutaneous pigmentation, hamartomatous polyps What are the main characteristics of Peutz-Jeger syndrome? Autosomal dominant Is Peutz-Jeger a dominant or recessive condition? Loss of APC gene What causes Familial AdenomatousPolyposis? Tubular adenomas in patients who are in their teens and twenties What is the main clinical feature of Familial AdenomatousPolyposis? Classic, Attenuated, Gardner Syndrome, Turcot Syndrome What are the four subtypes of Familial AdenomatousPolyposis? They do not arise from preexisting polyps From which type of polyp does the carcinoma from HNPCC arise? Proximal colon In which region does HNPCC usually manifest itself in the colon?

  43. Urologic Tumors Intercalated cells From what type of cell do oncocytomas originate? Tuberous sclerosis With what disease are angiomyolipomas of the kidney associated? Convential Renal Cell Carcinoma With what kind of tumor is the VHL gene associated with? Renal vein Where is a common site of metastasis of renal cell carcinomas? Medulla or cortex (peripherally) Where are renal cell carcinomas usually located in the kidney? They rarely metastasize How quickly do chromophobe carcinomas metastasize? Collecting Duct Carcinoma Which type of renal carcinoma is predominantly located in the pelvis of the kidney? Poor What is the prognosis of a sarcomatoid carcinoma of the kidney?

  44. Urologic Tumors Transitional Cells From what type of cells do urothelial carcinomas derive? Urothelial carcinoma What is the most common type of bladder cancer? Papilloma Grades I-III What are the four grades of urothelialneoplasms? Adenocarcinoma, squamous cell What are the 2 other major types of bladder cancer? Schistosomiasis What causes squamous cell carcinoma of the bladder? 0-10 (the two most common patterns, scaled 0-5); 7+ suggests action is surely required What is the range of scores on the Gleason scale? Chemotherapy – it is quite chemosensitive How is testicular cancer treated? Osteoblastic activity What is the general pattern of prostate cancer metastasis to the bone?

  45. Gynecologic Tumors Biopsy – it could be a sign of malignancy What should be done with leukoplakia? HPV (16 & 18, of course) What is the main cause of vulvar and vaginal squamous carcinomas? No Is Paget’s disease invasive? DES exposure to the mother of the affected patient What is the main cause of vaginal adenocarcinoma? Strains 16 & 18 affect Rb and p53 How does HPV cause cancer? The T-zone Where does most cervical cancer occur? Endometrial What is the most common type of female GU cancer? It’s asymptomatic What is the main symptom of CIN?

  46. Gynecologic Tumors Excess estrogen without progesterone What is the pathophysiology of endometrial cancer Excess estrogen production in the fat cells How is obesity related to endometrial cancer? It can be pre-cancerous Is there a relationship between endometrial hyperplasia and endometrial carcinoma? Abnormal uterine bleeding (especially post-menopausal) What is the main presenting symptom of endometrial carcinoma? Adenocarcinoma What type of cancer is endometrial carcinoma, usually? Often bilateral Is ovarian cancer uni- or bilateral? CA125 – it is nonspecific What marker can be used with ovarian cancer? Is it specific? Surface epithelium From which tissue do ovarian tumors generally derive?