Neoplasia Flashcards
What is cancer?
Genetic disorder caused by DNA mutations that are acquired spontaneously (usually) or induced by environ. insult. Also, frequently show epigenetic markers, such as focal increases in DNA methylation and histone alteration.
What are the hallmarks of cancer?
- Self-sufficiency
- Lack of response to growth inhibitors
- Evasion of cell death
- Limitless replication
- Angiogenesis
- Invade local tissues and spread
- Reprogramming of metabolic pathways
- Abilitiy to evade immune system
What is a benign tumor?
One that is thought to remain localized and is amenable to surgical removal. Can still be deadly
What is a malignant tumor?
Cancer, Adhere to any part that they seize. The lesion can invade and destroy adjacent structures and spread to distant sites to cause death.
What are the two basic components of tumors?
- Parenchyma - the part that is the transformed cells.
2. Stroma - the host derived non-neoplastic tissue and blood vessels that support the tumor.
What is a fibroma?
A bengin tumor arises in fibrous tissue
What is a chondroma?
A benign tumor arising in cartilaginous tissue
What is an adenoma?
Benign epithelial neoplasms producing gland patterns.
What is a papilloma?
Benign epithelial neoplasms grown on any surface that produce finger-like fronds.
What is a polyp?
A mass that projects above a mucosal surface to form a macroscopically visible structure
Malignant neoplasms arising in solid mesenchymal tissues are called?
Sarcomas
Malignant neoplasms of epithelial cells are called?
Carcinomas, regardless of which epithelial tissue.
Malignant mesenchymal cells of the blood are called?
Leukemias or lymphomas
What are adenocarcinomas?
Carcinomas that grown in glandular patterns
What are squamous cell carcinomas?
Carcinomas growing as squamous cells.
Tumors showing various types of tumors undergo what process?
Divergent diversification
What is a teratoma?
Special mixed tumor that contains recognizable features of more than one germ cell layer.
In general, what characteristics describe benign tumor?
Genetically simply, harboring rewer mutations than cancers, and genetically stable, changing little in genotype over time
What are the four fundamental features by which benign and malignant tumors can be distinguished?
Differentiation and anaplasia
Rate of Growth
Local Invasion
Metastasis
What is differentiation?
Refers to the extent to which they resemble the normal forebears morphologically and functionally.
Are well-differentiated cells a characteristic of malignant tumors?
They can be, but are more characteristic of benign tumors.
What is important about well-differentiated tumors
They retain a lot of the properties that the original tissue had.
Malignant tumors composed of undifferentiated cells are said to be?
Anaplastic
Is anaplasia associated with pleomorphism?
Yes
What is pleomorphism?
Variation in size and shape, with hyperchromatic staining, and mitoses often are numerous and distinctly atypical.
The more/less rapidly growing and the more/less anaplastic a tumor, the more/less likely it is to have specialized functional activity?
More rapidly growing, more anaplastic tumor, less likely to have specialized function
What is dysplasia?
Disorderly but non-neoplastic proliferation. Typically encountered in epithelial lesions. It is the loss of uniformity of individual cells and in their architectural orientation.
What is the growth rate for more benign tumors?
The grow slowly. Vs cancer which grows rapidly (to distant sites)
The growth rate of malignant tumors correlates inversely with what characteristic?
Their level of differentiation
What is the cancer stem cell hypothesis?
That, like human stem cells, cancer stem cells divide into the cancer and a cancer stem cell. So eliminating the cancer requires elimination of cancer stem cells, which are drug resistant.
Cancer cells grow by?
Progressive infiltration, invasion, destruction, and penetration of the surrounding tissue.
Next to ability to metastasis, what is the distinguishing characteristic of cancer?
Local Invasiveness
What are metastases?
Secondary implants of tumor that are discontinuous with primary tumor
In general, the more/less anaplastic and larger/smaller the primary neoplasm, the more/less likely is metastatic spread?
The more anaplastic and larger, the more likely
What are the three ways in which malignant tumors spread?
Seeding within the body cavities
Lymphatic spread
Hematogenous spread
Spread by seeding is particularly characteristic of what?
Ovarian Cancers
Lymphatic Spread is more typical of carcinomas or sarcomas?
Carcinomas
Hematogenous spread is more typical of carcinomas or sarcomas?
Sarcomas
What is a sentinel lymph node?
The first lymph node to receive metastases from cancers, typically identified with radiologic dye.
What are the most frequently involved secondary tumors in hematogenous spread?
Liver and lungs
What is the primary cause of sporadic cancers?
environmental factors
How old are most people that die from cancer?
55-75
What are the three categories of hereditary cancer?
Autosomal Dominant (Retinoblastoma) Autosomal Recessive (Xeroderma Pigmentosum) Uncertain Inheritance (Majority)
What are acquired preneoplastic lesions?
Acquired conditions which predispose an individual to cancer. i.e. squamous metaplasia and dysplasia of bronchial mucosa
Endoemtrail hyperplasia and dysplasia
What are the four classes of normal regulatory genes involved in cancer development?
Growth-Promoting Proto-Oncogenes, Growth-inhibiting tumor suppressor genes, Genes involved in apoptosis, Genes involved in DNA Repair
What are the two categories of tumor suppressor genes?
Guardians and governors
What are the three common types of nonrandom structural abnormalities in tumor cells?
- Balanced Translocation
- Deletions
- Cytogenetic Manifestations of Gene Amplification
What is miRNA?
They participate in neoplastic transformation either by increasing expression of oncogenes or reducing the expression of TSGs.
How does epigenetics factor into cancer cells?
Cancer cells are characterized by hypomethylation and selective promoter-localized hypermethylation
What has genome-wide hypomethylation been linked to?
Chromosomal Instability
What is the concept of tumor progression?
While tumors start monoclonal, as they become clinically evident, parts of the tumor will develop different charcteristics (becoming genetically different) that allow it to become more malignant.
How is self-sufficiency linked to growth factors?
They can secrete their own. They can tell the stroma to secrete their own.
What is the RAS protein?
Most commonly mutated proto-oncogene in tumors. 30% of all tumors. Normal RAS flips between on and off state, signaling active proliferation when on.
What is the MYC protein?
It can activate or repress other transcription genes.
What do CKD-Cylcin complexes do?
Phosphorylate crucial target proteins that drive the cell cycle. Should decline rapidly once they act. But in cancers, they don’t.
What types of cancer is Cyclin D mutation common in?
Esophagus, breast, live, and lymphomas
What is required for the development of Familial Retinoblastoma?
Two hits to one allele of RB
What are the four key regulators of cell cyle?
Cyclin D, CDK2A, CDK4, Rb
What is the role of p53?
It is the promotor of apoptosis in response to anoxia, DNA damage or stress.
What percentage of tumors have p53 biallelic loss?
70%
What is TGF-beta?
A cell cycle inhibitor
What is the extrinsic pathway of cell death?
Fas binds FasL, downstream activating Caspase-8, leading to cleavage of DNA
What is intrinisc pathway of cell death?
Loss of integrity of the mitochondrial membrane through the BCL2 proteins.
What is the typical role of BCL2 proteins in cancer cells?
A mutation causes an overexpression of BCL2 compared to BCL-X allows the cell to survive.
What is needed for limitless replicative potential?
Reactivation of telomere maintenance. Common in nearly all tumro
What is mechanism by which hypoxia triggers angiogenesis in tumors?
Hypoxia activates HIF on transcription of pro-angiogenic factors, leading to creation of VEGF.
What are the four steps of the metastatic cascade?
Loosening of tumor cells (loss of E-cadherin)
Degradation of basement membrane and connxtv tissue
Changes in attachment of tumor cells to ECM proteins
Locomotion, propelling tmor through basemet membranes and zones of matrix proteolysis
What is the Warburg Effect?
Many cancers adopt aerobic glycolysis instead of mitchondrial ATP production, even though there is oxygen present
What are the fastest grower tumors?
tumors that use aerobic glycolysis for energy
What is the difference between direct-acting and indirect-acting carcinogens?
Direct-acting are in the form needed to cause damange. Indirect must be converted, such as smoke.
What is an example of an oncogenic RNA Virus?
HTLV-1
What is an example of DNA oncogenic viruses?
HPV and EBV
How does EBV work?
Several oncogenic protein products activate normal B ell proliferation pathways. Continues immune response eventually leads to the development of lymphoma.
What bacteria associated with cancer?
H. pylori frequently assocaited with gastric cancers by polyclonal B cell proliferations and eventually monoclonal B cell tumor (malt lymphoma)
What is cachexia?
Progressive loss of body fat and lean body mass, accompanied by weakness, anorexia, and anemia.
What is paraneoplastic syndrome?
Systemic symptoms not explained by tumor spread of by hormones appropriate to tissue.
What are the five adjectives Nichols uses to describe neoplasms?
Autonomous Clonal Irreversible Benign Malignant
What is a sessile polyp?
A falt polyp
What is a pedunculated polyp?
One that is on a stalk on an epithelial surface
What is desmoplasia?
Formation of abundant fibrous stroma by some carcinomas, which is a reactive process
What are the six hallmarks of cancer
Sufficient individuals evade all invasions
When RB is phosphyrlated by CDK-Cyclin D complex, what does it release from it’s grasp?
Transcription Factor E2F
What are several tumor suppressor genes?
NF-1/2 (neurogibromatosis)
Von Hippel Lindau
TGF-Beta - pancreatic cancer
Patched (PTCH) - BASAL CELL CARCINOMA OF SKIN
How does Von Hippel Lindau TSG work?
It causes ubiquitination of Hypoxia-inducible Factor-1, preventing the stimulation of VEGF and PDGF, thus preventing angiogenesis
What are the essential features of RB?
RB typically is bound to E2F. When phosphorylated, it releases E2F, causing E2F (a transcription factor) to stimulate cell proliferation.
What are the essential features of APC tumor suppressor gene?
It controls intestinal stem cell proliferation through WNT signaling. It breaks down beta-catenin, so that it can’t bind to transcription factor TCF which drives cell proliferation. Common defect in colon cancers.
What are essential features of p53?
It binds to bad DNA, deciding between apoptosis and repair. Common mutation in cancers of all types.
What is NF-1?
Activates GTPase, creating GDP that binds to RAS, inactivating it.
What is Von Hippel Lindau?
Causes ubiq. of HIF, which prevents PDGF AND VEGF from accumulating (so that the cancer cannot undergo angiogenesis.
What is HER2?
An EGFR receptor overexpressed in 20 percent of breast cancer.
What is K-RAS?
Codes for a GTPase in cytoplasm on the inner side of the cell membrane bound to EGFR. Carries out signal transduction from cytoplasm to nucelus when EGFR binds growth factors, signalling cell proliferation.
What are the nine type of cancer caused bys moking?
Lung, mouth, pharynx, larynx, esophagus, stomach, pancreas, kidney, bladder
What are the four most common causes of cancer death in the uS?
Lung, breast/prostate, colon
5 most common causes of cancer
Smoking, obesity, alcohol, diet, HPV
What is Cachexia?
Cachexia is a common problem associated with cancer, late-stage heart failure and AIDS. It involves wasting away through severe weight loss
What is a paraneoplastic syndrome?
They are symptoms commonly seen in cancer that cannot be attributed to the cancer itself or the hormones it may secrete.
What is tumor grade?
A pathologist topic that refers to how anaplastic a tumor cell may be.
What is tumor stage?
A radiologist issue, referring to anatomic extent of tumor, primary size, extent of lymph node and distant metastases
What is cytology biopsy?
Sample of cells exfoliated or aspriated from the body
How do BRCA gene mutations lead to early breast cancer?
BRCA are common in DNA repair pathways. Germline mutations lead to breast cancer because they then don’t regulated DNA repair.
How does the t(14:18) translocation lead to cancer?
It results in the fusion of BCL2 gene from chromosome 18 with actie IgH locus on Chromosome 14 resulting in overproduction of anti-apoptotic BLC2
What normally inhibits angiogenesis?
Thrombomodulin and destruction of HIF1 (by VHL)
What turns off VHL, allowing HIF?
Hypoxia
What does HIF trigger?
VEGF production and growth of irregular leaky blood vessels.
What is the angiogenic switch?
Mediated by HIF, basic FGF, loss of p53, and decreased thrombomodulin-1
What drug inhibits angiogenesis?
Bevacizumab
Why does bevacizumb have limited efficacy towards cancer?
It prevents the growth of a large cancer. However, millions of tiny cancers can still have a lethal effect
What are the four stages of tumor invasion?
Detachment of tumor cells from each other (downregulate E-cadherin and catenin)
Degradation of the basement membrane by MMPs
Attachment of tumor cell to basement membrane by laminin and fibronectin
Migration of malignant cells through interstitium via autocrine motility factor
What is tumor embolus?
Tumor cells that invade veins, pass through the right heart and go the lungs. They stop and elicit formation of blood clot around them (organized by fibroblasts)
What is the mechanism for metastatic organ tropism?
Having multiple adhesion factors that are characterized for other cell organ types, like CXCR4 and CCR7
In carcinogens, what are initiators? promoters?
Initiators cause mutations, which become irreversible in progeny of the cell if not reversed.
Promoters cause reversible proliferation of inititated cells.
What are direct vs indirect carcinogens?
Direct carcinogens are in their active-cancer forming form. Typically electrophiles.
Indirect need metabolic activation commonly by p450-dependent mono-oxygenases. Examples are estrogen, alcohol, anti-cancer drugs, asbestos
What is the important characteristic of radiation carcinogens?
They have long latent periods. UV causes skin cancer. Radiation therapy leads to sarcomas. Nuclear power leaks lead to thyroid cancer
What are common microbial carcinogens?
HPV (cervical cancer)
HEP C AND B - hepatic cancer
EBV- lymphoma
Helicobbacter pylori - gastric carcinomas
How does the anti-tumor immune surveillance work?
Your immune system recognizes oncogenic viral products, antigens and altered cell surface glycolipids or glycoproteins.
What growth factor do tumors secrete that is an immunosuppressant?
TGF-beta
What are direct effects of tumors?
obstruction (ie intestines), bleeding or infection. they can infarct or rupture , or compress an artery or vein
What is hypercalcemia?
most common indirect effect of cancer. when caused by parathyroid-hormone-related protein (pthrp). symptoms are squamous cell carcinoma, nausea, vomiting, constipation, polyuria, disorientation, lethargy and seizures
What is cushing syndrome?
pituitary adenomas secreted ACTH. weight gain, obesity, fat deposition (moon face), weakness, HTN, glucose interolance, depression,
What is carcinoid syndrome?
Cutaneous flushing, diarrhea, cramps, nausea, vomiting, cough,
What are the serum tumor markers for cancer/
PSA, CA-125, CA19-9 HCG, AFP, CEA, Igs.
