Robbins Ch 7 - Neoplasia

The age for cancer death In women is: in men is:

- 40-90 years - 60-79 years

What genes in women with inherited mutations have a threefold incidence of breast cancer compared to women born before 1940?

- BRCA1 - BRCA2

3 function of PET scan

- Blood flow - Oxygen use - Sugar metabolism

Syndromes involving defects in the homologous recombination DNA repair system constitute a group of disorders:

- Bloom Syndrome - ataxia-telangiectasia - Fanconi Anemia ----characterized by hypersensitivity to DNA-damaging agents, such as ionizing radiation.

4 function of p53 protein

- Causes cell-cycle arrest at the G1-S checkpoint - Repair DNA damage - Causes cellular senescence, - Causes apoptosis

Characteristics of loss of polarity in differentiations and anaplasia:

- Cellular orientation is highly disturbed - Tumor cells grow in an anarchic, disorganized fashion

Explain Two-hit-hypothesis

- Children inherit one defective copy of the RB gene in the germline (the first hit), and the allele from the other parent is normal - Retinoblastoma develops when the normal RB allele is mutated in retinoblasts as a result of a spontaneous somatic mutation (the second hit) - individuals inheriting a germline defect in one RB allele develop unilateral or bilateral retinoblastoma - In sporadic cases both normal RB alleles must undergo somatic mutation in the same retinoblast (two hits).

3 acquired conditions that predispose to cancer

- Chronic inflammations (H. pylori infection - gastritis - gastric cancers) - Precursor lesions (Barrett esophagus, squamous metaplasia, endometrial hyperplasia) - Immunodeficiency states (Predispose to certain lymphomas and carcinomas)

Tumor marker CA-19-9:

- Colon cancer - Pancreatic cancer

3 Characteristics of Benign and Malignant Neoplasms

- Differentiation and Anaplasia - Local Invasion - Metastasis (Pathways of Spread)

3 factors of cancer cell replication potential:

- Evasion of senescence - Evasion of "mitotic crisis" (cell death) - Capacity for self-renewal

Characteristics of central necrosis in differentiations and anaplasia:

- Growing tumors need blood too - Rapidly growing tumors out grow their blood supply and develop central areas of ischemic necrosis

4 classes of normal regulatory genes:

- Growth promoting - Growth inhibiting - Apoptosis - DNA repair

Oncogenic DNA Viruses: Causes:

- HPV 16 & 18 - Squamous cell carcinoma of the cervix, anogenital region, head and neck;

An example of cancer that is curable: An example of cancer that is fatal:

- Hodgkin Lymphoma - Pancreatic adenocarcinoma

Oncogenic RNA Viruses: Causes:

- Human T-Cell Leukemia Virus Type 1 (HTLV-1) - Adult T-cell leukemia/lymphoma

What happens in DNA repair in the molecular basis of cancer?

- Impair the ability of a cell to recognize and repair nonlethal genetic damage - Leads to an accelerated rate of mutation acquisition, "genomic instability"

Compare and Contrast: Mitotic Crisis

- In germ cell, as the cell divides, telomare length stayes the same - In stem cells, as the cel divides, their telomere length shortens - In somatic cells, as they divide, their telomere shorten until they ryn out of telomere so they undergo mitotic crisis - In cancer cells they arise from somatic cells and able to evade mitotic crisis, thus activating telomerase length

7 Best established environmental factors affecting cancer risk are:

- Infectious agents - Smoking - Alcohol consumption - Diet - Obesity - Reproductive history - Environmental carcinogens

3 characteristics of Malignant Tumors

- Invasion and destruction of adjacent tissues - Spread to distant sites (metastasis) - Cause death

Likelihood of metastasis correlates with 4 things

- Lack of differentiation - Aggressive local invasion - Rapid growth - Large size

Which 2 cancer arise in blood-forming cells?

- Leukemia - Lymphomas

Tumor marker alpha feto protein:

- Liver cancer - nonseminomatous germ cell tumor of testis

Ability to invade tissues, a hallmark of malignancy, occurs in four steps:

- Loosening of cell-cell contacts - Degradation of ECM - Attachment to novel ECM components - Migration of tumor cells

The antiproliferative effect of Retinoblastoma is repealed in cancers through a variety of mechanisms, including:

- Loss-of-function mutations affecting RB - Viral oncoproteins that bind and inhibit RB

Tumor marker carcinoembryonic antigen:

- Lung - heart - stomach - pancreas - colon

2 function of Flow Cytometry:

- Measure of individual cell characteristics; antigens - Lymphoma protocols

Smoking causes Cancer of 7 organs:

- Mouth - pharynx - larynx - esophagus - pancreas - bladder - 90% of lung cancer deaths

Neoplasm means: Tumor means: Oncos means: Study of tumors or neoplasms is:

- New growth - Neoplasm - Tumor - Oncology

Alcohol consumption, "abuse" causes cancer of 4 organs

- Oropharynx - Larynx - Esophagus - Hepatocellular carcinomas

Teratoma originate from totipotent germ cells in 3 organs:

- Ovary - Testis - Midline embryonic rests

3 Morphologic changes associated with anaplasia:

- Pleomorphism - Abnormal nuclear morphology - Mitoses - Loss of polarity - Central necrosis

The metastatic site of many tumors can be predicted by the location of the which tumor? Many tumors arrest in the first capillary bed they encounter e.g. are:

- Primary tumor - Lungs & Liver

What are the two most common cancers in men and women?

- Prostate - Breast

3 functions of Immunohistochemistry:

- Provides for categorization of undifferentiated malignant tumors - Allows determination of site of origin of metastatic tumors - Can Detect molecules that have prognostic or therapeutic significance

What are proposed effects of inflammation?

- Release of factors that promote proliferation - Removal of growth suppressors - Enhanced resistance to cell death - Inducing of angiogenesis - Activating invasion and metastasis - Evasion of immune destruction

3 Pathways of Metastatic Spread

- Seeding of Body Cavities and Surfaces - Lymphatic Spread - Hematogenous Spread

All cancers display 8 fundamental changes in cell physiology; these are considered the hallmarks of cancer

- Self sufficiency in growth signals - Insensitivity to growth-inhibitory signals - Altered cellular metabolism (a switch to aerobic glycolysis, "Warburg effect") - Evasion of apoptosis - Limitless replicative potential (immortality) - Sustained angiogenesis - Ability to invade and metastasize - Ability to evade host immune response

Tumor marker Neuron specific enolase:

- Small cell lung cancer - Neuroblastoma

Capacity for self-renewal are 2 types

- Symmetric division (Both daughter cells remain stem cells) - Asymmetric division (Only one daughter cell remains a stem cell)

Tumor marker Human chorionic gonadotropin:

- Trophoblastic tumors - nonseminomatous testicular tumors

4 characteristics of benign tumor:

- Will remain localized - Will not spread to other sites; metastasize via blood, etc. - Is amenable to surgical resection - The patient generally survives

3 classifications of benign tumors of epithelial origin is based on:

- cell or origin - microscopic pattern - macroscopic architecture

What is the mechanism of chemical carcinogenesis?

- have a highly reactive electrophile group that damages DNA leading to mutation - do not require metabolic conversion to be carcinogenic - after exposure to mutagen or initiator, tumor genesis can be enhanced by exposure to promoters - stimulate proliferation of mutated cells

What is occurring in radiation carcinogenesis?

- ionizing radiation causes chromosome breakage, translocations and point mutations leading to genetic damage and carcinogenesis - UV rays form pyrimidine dimers in DNA

A benign tumor of mesenchymal origin has a suffix of:

-oma

3 Steps Involved in Chemical Carcinogenesis:

1. Initiation: exposure to a sufficient dose of a carcinogenic agent 2. Permanent / irreversible DNA damage (mutations) 3. A promotor induces cells to become neoplastic (contributes to additional mutations)

All tumors have two basic components:

1. Neoplastic cells in tumor parenchyma 2. Reactive stroma made up of connective tissue, blood vessels and cells

The most important influence on the likelihood of being afflicted with cancer; Carcinomas is age:

> 55

The neoplastic epithelial cells grow in a glandular pattern is:

Adenocarcinoma

A benign epithelial neoplasm derived from glands is:

Adenoma - may or may not form glandular tissue

A polyp with glandular tissue:

Adenomatous polyp

A class of tumor suppressors that function by down regulating growth promoting signaling pathways is:

Adenomatous polyposis coli (APC)

Lack of differentiation is called:

Anaplasia

Malignant neoplasms that are composed of poorly differentiated cells are said to be:

Anaplastic

Even if a solid tumor possesses all of the genetic aberrations that are required for malignant transformation, it cannot enlarge beyond 1 to 2 mm in diameter unless it has the capacity to induce:

Angiogenesis

Accumulation of neoplastic cells may result...from mutations in the genes that regulate:

Apoptosis

Mutated familial breast cancer genes:

BRCA1 and BRCA2

Why are anaplastic tumors difficult to diagnose?

Because anaplastic tumors do not resemble a well differentiated tissue -- require special stain

Tumor marker TP53 mutants in urine:

Bladder cancer

Which cancer are often spread at diagnosis and are always taken to be malignant?

Blood cancers (derived from blood forming cells)

Breast carcinomas preferentially spread to what?

Bone

Tumor marker CA-15-3:

Breast cancer

Epstein-Barr Virus causes:

Burkitt Lymphoma (African form)

Progressive loss of body fat and lean body mass, accompanied by profound weakness, anorexia, and anemia, that is caused by release of factors by the tumor or host immune cells is called:

Cachexia

The intrinsic pathway of apoptosis caspases is most frequently disabled in:

Cancer

What must be eliminated to eradicate the tumor?

Cancer stem cells

Cancer from epithelial cell origin (any of the germ layers) is:

Carcinoma

A pre invasive stage of cancer that commonly occurs in the epithelium of the skin, breast and cervix is called:

Carcinoma in situ

Display the cytological features of malignancy without the invasion of the basement membrane:

Carcinoma in situ

Is "one step removed" from invasive cancer and With time, most penetrate the basement membrane:

Carcinoma in situ

When dysplastic changes involve the full thickness of the epithelium but does not penetrate the basement membrane, it is called:

Carcinoma in situ -- often a precursor to malignant transformation

A benign tumor arising from cartilage is:

Chondroma

Malignant tumor arising from cartilage is:

Chondrosarcoma

A heterotopic (occupying an abnormal place) rest of cells - benign tumors, found in abnormal locations is called:

Choristoma

Tumor marker TP53, APC, RAS mutants in stool and serum:

Colon cancer

Benign epithelial derived neoplasms which form cystic masses:

Cystadenomas

Once a tumor has been established, its' evolution (growth and progression) follows what selection?

Darwinian selection

The formation of abundant collagenous stroma is called:

Desmoplasia

The extent to which neoplastic parenchymal cells resemble the corresponding normal parenchymal cells, both morphologically and functionally is called:

Differentiation

Cellular adaptation of disordered growth:

Dysplasia

What appears to be the dominant risk factors for most cancers?

Environmental influences

The Warburg Effect:

Even in the presence of ample oxygen, cancer cells demonstrate a distinctive form of cellular metabolism characterized by high levels of glucose uptake and increased conversion of glucose to lactose (fermentation) via the glycolytic pathway.

A benign tumor arising from fibrous tissue is:

Fibroma

Malignant tumor arising in fibrous tissue is:

Fibrosarcoma

A radioactive analog (a "tracer") of glucose given to patients pre-scan that accumulate in areas of the body that have a high glucose uptake is called:

Fluorodeoxyglucose

Helicobacter pylori causes:

Gastric adenocarcinoma

Genetic aberrations that increase mutation rates are very common in cancers and expedite the acquisition of (additional) mutations that are required for transformation and subsequent tumor progression:

Genomic Instability

Determined by cytologic appearance; based on the idea that behavior and differentiation are related, with poorly differentiated tumors having more aggressive behavior. This is called:

Grading

A disorganized, benign masses composed of cells indigenous to the involved site and considered a neoplasm:

Hamartoma

What is the exception of a benign tumor that does not create a tissue plane or easily excisable?

Hemangiomas

Typical spread of sarcomas; seen in carcinomas too is called:

Hematogenous Spread

Hepatitis B and C Viruses causes:

Hepatocellular carcinoma

What triggers angiogenesis through transcription of the proangiogenic factor, vascular endothelial growth factor (VEGF)?

Hypoxia

What is the most reliable feature that differentiates cancers from benign tumors next to metastases?

Invasion -- most malignant tumors do not recognize anatomical boundaries

Once dysplastic tumor cells have breached the basement membrane, it is called:

Invasive

Malignant tumor arising from smooth muscle is:

Leiomyosarcoma

Patients with which syndrome inherit one defective copy of p53 and have a very high incidence of a wide variety of cancers:

Li-Fraumeni syndrome

The growth of cancers is accompanied by progressive infiltration, invasion, and destruction of the surrounding tissue, whereas nearly all benign tumors grow as cohesive expansile masses that remain localized to their site of origin and lack the capacity to infiltrate, invade, or metastasize to distant sites:

Local invasion

Tumor marker TP53, RAS in sputum and serum:

Lung cancer

What the two most common causes of death by cancer in men and women?

Lungs in both

Most common pathway for initial Spread of carcinomas; seen in sarcomas too is:

Lymphatic Spread

Atypical, bizarre mitotic figures with tripolar - multipolar spindles is called:

Malignancy

Tumor marker calcitonin

Medullary carcinoma of thyroid

A cellular adaptation to stress often found in areas associated with tissue damage, repair and regeneration is called:

Metaplasia

The replacement of one type of cell with another type is called:

Metaplasia

The spread of a tumor to sites that are physically discontinuous with the primary tumor, and unequivocally marks a tumor as malignant is called:

Metastasis

Divergent differentiation of a single neoplastic clone; divergence often remains within the same germ layer is called:

Mixed tumor

Tumor marker Immunoglobulins:

Multiple myeloma

An abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change:

Neoplasm

When does seeding of body cavities and surfaces occur?

Occurs when a malignant neoplasm penetrates into a natural "open field" lacking physical barriers

Genes associated with cell growth which have mutated and promote autonomous cell growth in cancer is called:

Oncogenes

Oncogenes encode proteins which promote cell growth in the absence of normal signals is called:

Oncoproteins

Tumor marker CA 125:

Ovarian cancer

Commonly differentiate along ectodermal lines creating a cystic tumor lined with hair bearing skin, sebaceous glands and tooth structures?

Ovarian cystic teratoma (dermoid cyst)

What scan measures important body functions, such as blood flow, oxygen use, and sugar (glucose) metabolism, to help doctors evaluate how well organs and tissues are functioning?

PET scan

Tumor marker TP53, RAS mutants in stool and serum:

Pancreatic cancer

A benign neoplasm with papillary projections within a cystic neoplasm is:

Papillary cystadenomas

Benign epithelial neoplasm producing micro / macroscopic fingerlike or warty projections from epithelial surfaces is:

Papillomas

Symptom complexes in individuals with cancer that cannot be explained by tumor spread or release of hormones that are indigenous to the tumor cell of origin is called:

Paraneoplastic syndromes

Which syndrome may be the earliest manifestation of an occult neoplasm and can cause significant clinical problems; may be lethal?

Paraneoplastic syndromes:

In the subject of genomic instability, what can greatly increased risk for the development of cancer?

Persons with inherited mutations of genes involved in DNA repair systems

A mixed tumor of the salivary glands; produces epithelial components and a myxoid (mucinous) stroma that may contain cartilage or bone is called:

Pleomorphic adenoma

Any macroscopic projection (benign or malignant) above a mucosal surface:

Polyp

A tumor of epithelial origin does not appear morphologically like normal epithelium; this is called:

Poorly-differentiated

Tumor marker Prostate-specific antigen:

Prostate cancer

Tumor marker prostatic acid phosphate:

Prostate cancer

Basement membranes and interstitial matrix degradation is mediated by ________ secreted by tumor cells and stromal cells

Proteolytic enzymes

Genes associated with cell growth which have not yet been mutated is called:

Proto-oncogenes

What happens in Growth promoting in the molecular basis of cancer?

Proto-oncogenes and Mutations cause a "gain of function"

A mucinous appendicial carcinoma or mucinous ovarian carcinoma invades the peritoneum and fills the peritoneal cavity with a gelatinous neoplastic mass called:

Pseudomyxoma peritonei

Cancer causing mutations occur in which genes?

Regulatory genes

Malignant tumor arising from striated muscle is:

Rhabdomyosarcoma

Cancer that arise in solid mesenchymal / connective tissues is:

Sarcoma

Soft and fleshy tumors are called:

Scant stroma

Stony hard desmoplasia (some breast cancers) is called:

Scirrhous

The first node in a regional lymphatic basin that receives lymph flow from the primary tumor:

Sentinel lymph node

A tumor is formed by the clonal expansion of a ____________ that has incurred genetic damage

Single precursor cell

The single most common cause of premature death in the USA is:

Smoking

Tumor cells resemble stratified squamous epithelium is:

Squamous cell carcinoma

Determined by surgical exploration or imaging, is based on size, local and regional lymph node spread, and distant metastases; this is called:

Staging

Growth and spread of a tumor are dependent upon the:

Stroma

A mixed tumor with neoplastic cells that belong to more than one germ cell layer is called:

Teratoma

What happens to cellular adaptations (hyperplasia, hypertrophy, metaplasia, etc.) once the stimulus is removed?

The tissue returns to its normal and original state

Which germ cells can differentiate into any of the cell types in the human body?

Totipotent germ cells

What is metastasis by lymphatic spread?

Transportation of neoplastic cells through the lymphatics

What contribute to the detection of cancer and in some instances are useful in determining the effectiveness of therapy or the appearance of a recurrence?

Tumor Markers

What happens in Growth inhibiting in the molecular basis of cancer?

Tumor suppressor genes and Mutations result in a "loss of function"

Which proteins form a network of checkpoints that prevent uncontrolled growth?

Tumor suppressor proteins

The role of tumor suppressor genes from studies of Retinoblastoma is explained by

Two-hit-hypothesis of oncogenesis

Undifferentiated malignant tumor means:

Unknown tissue origin

What are used to treat a number of advanced cancers and prolong the clinical course, but are not curative?

VEGF inhibitors

Hypoxia triggers angiogenesis through transcription of the proangiogenic factor, called:

Vascular endothelial growth factor (VEGF)

Which protein inactivates p53?

Viral oncoproteins

When a tumor of glandular epithelium morphologically resembles the epithelium from which it arose, it is called:

Well-differentiated

Patients with xeroderma pigmentosum have what defect?

a defect in the nucleotide excision repair pathway and are at increased risk for the development of cancers of the skin exposed to UV light, because of an inability to repair pyrimidine dimers.

What is the capsule of a benign tumor?

benign tumors grow and expand slowly, often developing a rim of compressed fibrous tissue -- Creates a tissue plane, making the tumor discrete, palpable and easily excisable.

Nonlethal genetic damage lies at the heart of:

carcinogenesis

Patients with hereditary non-polyposis colon cancer (HNPCC) syndrome have what defect?

defects in the mismatch repair system, leading to development of carcinomas of the colon. These patients' genomes show microsatellite instability, characterized by changes in length of short repeats throughout the genome.

Lack of differentiation (anaplasia) is a hallmark of:

malignancy

What does aerobic glycolysis provide in dividing tumor cells?

metabolic intermediates that are needed for the synthesis of cellular components, whereas mitochondrial oxidative phosphorylation does not

What is the intrinsic pathway of apoptosis?

mitochondrial; cytochrome c release activates caspases

Immunosuppressed patients have increased risk for development of cancer, particularly types caused by:

oncogenic DNA viruses

What protein controls the expression and activity of proteins involved in cell cycle arrest, DNA repair, cellular senescence, and apoptosis?

p53

What protein is the central monitor of stress in the cell and can be activated by anoxia, inappropriate signaling by mutated oncoproteins, or DNA damage

p53 protein

Where does seeding of body cavities most frequently occur?

peritoneal cavity

Tumor marker catecholamine & metabolites

pheochromocytoma tumors (adrenal gland)

What happens in Apoptosis in the molecular basis of cancer?

programmed cell death genes and result in less death/enhanced survival of cells

Pleomorphic tumor of the skeletal muscle is called:

rhabdomyosarcoma

Retinoblastoma exerts antiproliferative effects and regulates genes required for cells to pass through what mitosis phase?

the G1-S phase cell cycle checkpoint

The classification of tumors is based primarily upon:

the parenchymal component

Individuals with germline mutations of Adenomatous polyposis coli (APC) develop what?

thousands of adenomatous polyps in the colon during their teens-20's -- 100% will have colon cancer by age 40